Increased Plasma and Erythrocyte Selenium Concentrations but Decreased Erythrocyte Glutathione Peroxidase Activity after Selenium Supplementation in Children with Down Syndrome

ABSTRACT. An investigation was made of the activity of glutathione peroxidase (GSH-Px) in erythrocytes and the levels of selenium in plasma and erythrocytes before, during and after selenium supplementation in children with Down syndrome (DS). This subject is of interest since it has been suggested that selenium supplementation could enhance the GSH-Px activity in erythrocytes, probably leading to unproved protection against oxygen radicals, which might cause damage by lipid peroxidation, especially in the brain. Forty-eight children with DS were treated with selenium-rich yeast tablets (10 μg/kg body weight/day) for 6 months. The supplementation was well tolerated and no side effects were observed. Selenium supplementation resulted in increased concentrations of selenium both in plasma and erythrocytes, but decreased GSH-Px-activity in erythrocytes. Plasma and erythrocyte selenium levels had almost regained the initial values 12 months after termination of the supplementation. Erythrocyte GSH-Px activity, on the other hand, remained reduced and did not return to the presupplementation levels. Until we gain more knowledge about the biological functions of selenium in man and the role of oxygen metabolism in the development of presenile dementia in DS, universal selenium supplementation in DS patients cannot be recommended.     

Selenium in Plasma and Erythrocytes in Patients with Down's Syndrome and Healthy Controls

ABSTRACT. The mean plasma selenium concentration (P-Se) in 65 patients with Down's syndrome (DS) did not differ from that in 90 healthy controls. The concentration of selenium in the erythrocytes (E-Se) was higher in DS patients than in controls ( p <0.001). P-Se and E-Se increased progressively with age through childhood in both DS children and controls. The former children, however, started out with higher levels of E-Se and reached adult concentrations earlier (at 7-17 years) than controls (18 years). Adult DS patients and controls did not differ in their mean P-Se or E-Se concentration. There was a significant correlation between P-Se and E-Se both in DS patients and in controls. In DS patients each of these two variables was significantly correlated to glutathione peroxidase (GSH-Px) activity in erythrocytes. A sex difference in the DS children, but not in the controls, was observed with regard to P-Se and E-Se levels, these being higher in DS girls during childhood (0-17 years). This was in accordance with an earlier finding of higher GSH-Px activity in DS girls than in DS boys.     

Selenium supplementation in X-linked muscular dystrophy. Effects on erythrocyte and serum selenium and on erythrocyte glutathione peroxidase activity

The selenium concentrations in serum and erythrocytes and the erythrocyte glutathione peroxidase activity were determined in 15 boys with the Duchenne type and in 5 boys with the Becker type of X-linked muscular dystrophy before and during long-term selenium and alpha-tocopherol supplementation and compared with values in unsupplemented controls. The purpose of the treatment was to improve the muscular strength. Twelve of the 20 patients had pretreatment levels of selenium in serum that were within the 95% confidence limit of the unsupplemented control children. The values in 2 patients, both with the Duchenne type of muscular dystrophy, fell below this level. Selenium supplementation in a daily dose of 6 micrograms/kg/day for 6 months caused a substantial rise in both serum and erythrocyte selenium, suggesting suboptimal pretreatment body contents of selenium. The greatest increases in both serum and erythrocyte selenium were observed in subjects with initially low selenium levels. Only in 4 of the 20 patients did the selenium supplementation result in a significant rise in erythrocyte glutathione peroxidase activity. As no sure improvement was noted in muscular strength during this treatment period, the Se dose was increased to 20 micrograms/kg/day. This resulted in a further rise in both serum and erythrocyte selenium, but not in erythrocyte glutathione peroxidase activity.     

Selenium in plasma and erythrocytes in patients with Down's syndrome and healthy controls. Variation in relation to age, sex and glutathione peroxidase activity in erythrocytes

The mean plasma selenium concentration (P-Se) in 65 patients with Down's syndrome (DS) did not differ from that in 90 healthy controls. The concentration of selenium in the erythrocytes (E-Se) was higher in DS patients than in controls (p less than 0.001). P-Se and E-Se increased progressively with age through childhood in both DS children and controls. The former children, however, started out with higher levels of E-Se and reached adult concentrations earlier (at 7-17 years) than controls (greater than or equal to 18 years). Adult DS patients and controls did not differ in their mean P-Se or E-Se concentration. There was a significant correlation between P-Se and E-Se both in DS patients and in controls. In DS patients each of these two variables was significantly correlated to glutathione peroxidase (GSH-Px) activity in erythrocytes. A sex difference in the DS children, but not in the controls, was observed with regard to P-Se and E-Se levels, these being higher in DS girls during childhood (0-17 years). This was in accordance with an earlier finding of higher GSH-Px activity in DS girls than in DS boys.     

Plasma glutathione peroxidase after selenium supplementation in patients with reduced selenium state

The plasma glutathione peroxidase (GSHPx) activity was measured in normal adults and children and in patients with reduced selenium state because of dietary treatment of metabolic diseases (phenylketonuria or maple-syrup-urine disease) before and after selenium supplementation. Besides GSHPx (measured with t-butyl hydroperoxide, cumene hydroperoxide and hydrogen peroxide as acceptor substrates) the activity of glutathione S-transferase was estimated in plasma. Plasma GSHPx activity in healthy children was significantly lower than in healthy adults. In 11 dietetically treated patients with phenylketonuria or maple-syrup-urine disease the plasma GSHPx was reduced to about 17% of the values of healthy children of the same age. No glutathione S-transferase activity could be found in plasma of children in normal or reduced Se state.During administration of yeast rich in Se (200g Se/d) for 90 days 2 healthy adults showed no significant change of plasma GSHPx activity. During Se supplementation (75–100g Se/d) for 120–163 days 5 dietetically treated patients with PKU or MSUD exhibited a significant increase of plasma GSHPx activity within 2 days. The values reached a plateau after 1 to 3 weeks of supplementation and remained at this level within the following 4 to 5 months. Therefore, the activity of plasma glutathione peroxidase can be used as an indicator of short-term changes of selenium intake in selenium deficient individuals.Abbreviations (PKU) Phenylketonuria - (MSUD) maple-syrup-urine disease - (GSHPx) glutathione peroxidase - (t-BOOH) t-butyl hydroperoxide - (COOH) cumene hydroperoxide - (H₂O₂) hydrogen peroxide - (GSH) reduced glutathione With support of the Deutsche Forschungsgemeinschaft     

Influence of age on the selenium status in Belgium and The Netherlands

Plasma selenium concentration and glutathione peroxidase activity in red blood cells were determined in subjects from different age groups. The selenium level (mean +/- SD) found in infancy (0 to 6 months) was 2 +/- 0.6 micrograms/dl, with the lowest value of 1 microgram/dl observed in a 4-month-old infant. These levels were significantly lower (p less than 0.001) than the value of 9.5 +/- 1.1 micrograms/dl found in the adult group and 7.7 +/- 1.3 micrograms/dl found in the group of older children (2 to 15 yr). Younger children (6 to 24 months of age) had intermediate levels of 5 +/- 1.2 micrograms/dl. When the data were plotted on a logarithmic scale as a function of age, the figure shows clearly that the plasma selenium levels increase steadily with age throughout life after an initial drop at 60 to 90 days. There was a satisfactory correlation between the plasma selenium concentration and the enzyme glutathione peroxidase activity in the red blood cells (Spearman's p = 0.45, p less than 0.005). Although very low selenium values were observed, the enzyme glutathione peroxidase activity remained above 10 U/g hemoglobin (with only one exception) in all patients.     

Plasma and erythrocyte levels of trace elements and related antioxidant enzyme activities in low-birthweight infants during the early postnatal period

To discover the relationship between antioxidant enzyme activities and trace elements in lowbirthweight infants during the early postnatal period, we analysed catalase (CAT), CuZnsuperoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px) activities in erythrocytes, and compared them with Fe, Cu, Zn and Se levels in plasma, and Cu, Zn and Se levels in erythrocytes until 16 wk after birth. Thirteen low-birthweight infants whose mean birthweight and gestation were 1520 ±293 g and 32.0 ±2.8 wk were enrolled in this study. All infants were without chronic complications, well nourished, and predominantly fed standard formula or preterm formula based on cow's milk, commercially available in Japan. Cu and Zn levels in erythrocytes did not decline after birth, in contrast to a temporal decrease in plasma Zn. Erythrocyte CAT activity was significantly higher at 16 wk than that at birth or 4 wk of age. Erythrocyte CuZn-SOD activity did not change throughout the study period. Only Se in plasma and erythrocytes decreased remarkably after birth, which resulted in a significant decline in erythrocyte GSH-Px activity at 8 and 16 wk (11.2 ±2.0 and 11.0 ±1.1 U/g Hb) compared to that at birth (12.4 ±2.1 U/g Hb).

Conclusion: During the early postnatal period, erythrocyte CAT and CuZn-SOD activities did not decrease in formula-fed, low-birthweight infants. Japanese commercial formula not supplemented with Se, however, caused postnatal plasma and erythrocyte Se deficiency and a concomitant decline in erythrocyte GSH-Px activity in the same subjects.     

Macrocytosis and pseudoalbinism: manifestations of selenium deficiency

Selenium levels were low in four children receiving long-term total parenteral nutrition (TPN) who developed erythrocyte macrocytosis (3/4), loss of pigmentation of hair and skin (2/4), elevated transaminase and creatine kinase activities (2/4), and profound muscle weakness (1/4). Initial mean selenium levels in serum and hair were 38 +/- 11 (SEM) ng/mL and 0.34 +/- 0.13 micrograms/g, respectively. Mean serum vitamin B12, folate, and vitamin E levels were normal. Intravenous supplementation with selenium was begun daily at 2 micrograms/kg/day. After 3 to 6 months, serum selenium levels rose almost threefold to 81 +/- 22 ng/mL. During this same time, erythrocyte mean corpuscular volume fell from 115 +/- 8 fL to 88 +/- 7 fL in the three children with macrocytosis. After 6 to 12 months of supplementation, hair selenium content had increased threefold to 1.02 +/- 0.19 micrograms/g. The two children with decreased pigmentation became darker skinned and their hair color changed from blonde to dark brown; a third child's hair, which had been blonde, also became darker. Transaminase and creatine kinase activities returned to near normal in those affected and, in the one child with severe myopathy, muscle weakness improved. Erythrocyte macrocytosis and loss of skin and hair pigmentation are previously undescribed manifestations of selenium deficiency. We recommend routine supplementation of TPN solution with selenium to avoid the clinical and biochemical syndrome of selenium deficiency in patients receiving long-term TPN.     

Selenium Supplementation in X-linked Muscular Dystrophy

ABSTRACT. The selenium concentrations in serum and erythrocytes and the erythrocyte glutathione peroxidase activity were determined in 15 boys with the Duchenne type and in 5 boys with the Becker type of X-linked muscular dystrophy before and during long-term selenium and α-tocopherol supplementation and compared with values in unsupplemented controls. The purpose of the treatment was to improve the muscular strength. Twelve of the 20 patients had pretreatment levels of selenium in serum that were within the 95 % confidence limit of the unsupplemented control children. The values in 2 patients, both with the Duchenne type of muscular dystrophy, fell below this level. Selenium supplementation in a daily dose of 6 μg/kg/day for 6 months caused a substantial rise in both serum and erythrocyte selenium, suggesting suboptimal pretreatment body contents of selenium. The greatest increases in both serum and erythrocyte selenium were observed in subjects with initially low selenium levels. Only in 4 of the 20 patients did the selenium supplementation result in a significant rise in erythrocyte glutathione peroxidase activity. As no sure improvement was noted in muscular strength during this treatment period, the Se dose was increased to 20 μg/kg/day. This resulted in a further rise in both serum and erythrocyte selenium, but not in erythrocyte glutathione peroxidase activity.     

Selenium and vitamin E in mucoviscidosis

Selenium and vitamin E are two important components which protect membrane lipids from oxidative damage. Recently an abnormal fatty acid turnover in the membrane phospholipids was found in cystic fibrosis (CF). We studied vitamin E and selenium status in 26 CF children compared to a control group. we measured selenium concentration in plasma and erythrocytes using flameless atomic absorption. The measure of erythrocyte glutathione peroxidase activity allowed a functional assessment of selenium. Total plasma tocopherol concentrations (HPLC) were referred to total lipids. The vitamin E and selenium levels in not yet treated children (n = 6) were very low, with an important decrease in glutathione peroxydase activity. The antioxidative agents deficiency was mild in children with pancreatic enzyme replacement and vitamin E supplementation (n = 20). In the 2 groups, this deficiency was combined and may play a role in CF membrane abnormalities.     

Serum selenium levels in acute gastroenteritis of possible viral origin

Selenium, as an essential micronutrient, is required for the proper functioning of the immune system and its deficiency affects the occurrence, virulence, or disease progression of some viral infections. We conducted a study to determine the serum selenium levels of children with acute gastroenteritis of possible viral origin and the effect of the serum selenium levels on the severity and the morbidity of the disease. The study was performed prospectively on 109 children aged 2-24 months with diarrhea of less than 8 days' duration admitted to the Diarrheal Disease Training and Treatment Unit. Blood samples were taken for selenium measurement on admission and 7-10 days after the end of the disease. Forty-three healthy children formed the control group. The mean serum selenium level on admission (62.41 +/- 13.06 microg/dl) was significantly lower than the mean of the second samples 7-10 days after the end of the diarrhea (81.73 +/- 17.10 microg/dl). The mean of the control group was 74.36 +/- 10.75 microg/dl, which was lower than the mean of the second samples but higher than the first sample. The frequency of vomiting and purging on admission and at the control visit, duration of diarrhea on admission, total duration of diarrhea, dehydration, breastfeeding, sex of the patients, and severity score of the disease did not alter the serum selenium levels. No correlation was detected between serum selenium levels and the parameters above. Further studies about the changes in selenium status during infectious diseases and the effect of selenium status on related mortality and morbidity are required to determine if there is need for supplementation.     

The selenium status of children with phenylketonuria: results of selenium supplementation

The selenium status of children with phenylketonuria on a synthetic low phenylalanine diet was assessed. Correlation between blood selenium and red cell glutathione peroxidase was unsatisfactory (r = 0.65) due to the poor discrimination of red cell glutathione peroxidase with a low selenium diet. No symptoms of deficiency were observed. Supplementation with 50 micrograms per week of selenium as brewers yeast tablets over a period of 6 months significantly increased the blood selenium of the phenylketonuric children. Plasma Vitamin E levels were within normal limits. The supplementation effectively doubled their selenium intake to 15-17 micrograms per day, which is probably sufficient for this group with an adequate Vitamin E status, though considerably lower than the recommended minimum intake of 50 micrograms per day.     

The selenium status of children with phenylketonuria: Results of selenium supplementation

The selenium status of children with phenylketonuria on a synthetic low phenylalanine diet was assessed. Correlation between blood selenium and red cell glutathione peroxidase was unsatisfactory ( r = 0.65) due to the poor discrimination of red cell glutathione peroxidase with a low selenium diet. No symptoms of deficiency were observed. Supplementation with 50 μg per week of selenium as brewers yeast tablets over a period of 6 months significantly increased the blood selenium of the phenylketonuric children. Plasma Vitamin E levels were within normal limits. The supplementation effectively doubled their selenium intake to 15–17 μg per day, which is probably sufficient for this group with an adequate Vitamin E status, though considerably lower than the recommended minimum intake of 50 μg per day.     

Selenium status of New Zealand infants fed either a selenium supplemented or a standard formula

Objective: New Zealand soils are deficient in the essential micronutrient, selenium. New Zealand infants have low selenium levels at birth and experience a further decline if fed cows milk based formula. This study examined the selenium status of infants fed with a new commercially available selenium supplemented formula.
Methodology Forty-four newborn infants, whose mothers wished to formula feed, were randomized in an open controlled trial to be fed a commercially available selenium supplemented cows milk formula (containing 17 μg Se/L) or an unsupplemented formula (containing 4.6 μg Se/L). Cord, 1 and 3 month blood samples were obtained for selenium status (plasma and red cell selenium and glutathione peroxidase) and thyroid function.
Results Mean plasma selenium and glutathione peroxidase values were significantly higher in supplemented than unsupplemented infants at 1 month (unpaired t -tests; P <0.0001 and P = 0.001 respectively) and 3 months ( P <0.0001 and P = 0.0005). Analysis within treatment groups between time points (paired t -tests) showed that selenium supplementation prevented the fall in plasma selenium from birth to 1 month seen in unsupplemented infants and was associated with a rise in levels between 1 and 3 months ( P = 0.002).
Conclusions Supplementing cows milk formula with selenium to replicate the levels found in breast milk is nutritionally sound. Feeding from a few days of age with a formula containing 17 μg Se/L in infants with low selenium status at birth is sufficient to cause a rise to 80% of adult levels at 3 months of age.     

Protein carbonyls and lipid peroxidation products as oxidation markers in preterm infant plasma: associations with chronic lung disease and retinopathy and effects of selenium supplementation

The purpose of this study was to determine whether protein carbonyls and the lipid peroxidation product malondialdehyde (MDA) are elevated in plasma from very low birth weight (<1500 g) infants, whether they are affected by selenium supplementation, and whether they are associated with poor respiratory outcome or retinopathy. The study group comprised 173 infants enrolled in a randomized controlled trial of selenium supplementation. Plasma samples, collected before randomization, at 7 and 28 d after birth, and at 36 wk postmenstrual age, were analyzed for protein carbonyls and total MDA. Respiratory outcome was assessed as oxygen requirement at 28 d of age or 36 wk postmenstrual age and as number of days on oxygen. Protein carbonyl concentrations in very low birth weight infants were significantly higher than for adults but lower than for cord blood from term infants. Median values decreased significantly by 28 d, and there was no relationship with birth weight. MDA concentrations in very low birth weight infants overlapped the ranges for healthy adults and cord blood from term infants. They correlated positively with birth weight at 28 d but not at other times. Supplementation almost doubled plasma selenium concentrations, but carbonyls and MDA did not differ between the supplemented and unsupplemented groups. There were no significant differences in oxidant marker levels in infants who did or did not develop chronic lung disease or retinopathy. Protein carbonyls and MDA measurements in plasma do not show evidence of systemic oxidative stress in <1500-g infants and are not affected by selenium supplementation. Oxidative injury at sites such as the lung may be important in prematurity, but markers from such sites must be measured to relate to outcome and antioxidant supplementation.     

Zinc, copper, manganese, and selenium metabolism in patients with human growth hormone deficiency or acromegaly

This study was designed to evaluate trace metal metabolism in patients with known abnormalities of human growth hormone (hGH). The mean concentration of zinc in plasma and urine decreased in patients with hGH deficiency after hGH injection, whereas, after adenomectomy, in patients with acromegaly, zinc increased in plasma, remained the same in erythrocytes, and decreased in urine. There was a negative correlation between plasma zinc and serum hGH levels and a positive correlation between urinary zinc excretion and serum hGH levels in acromegaly. In hGH deficiency, the copper content remained unchanged in plasma and erythrocytes and rose in urine after treatment; however, in acromegaly, the copper content increased in plasma and remained unchanged in erythrocytes and urine after surgery. The mean concentration of erythrocyte manganese did not change significantly after treatment in patients with hGH deficiency or acromegaly, but the pre-hGH treatment level of erythrocyte manganese in hGH deficiency was lower than in the controls. Plasma selenium concentrations were decreased in hGH deficiency and increased in acromegaly patients after therapy. These results suggest that hGH affects the metabolism of zinc, copper, manganese, and selenium.     

Iron, zinc, copper and selenium status of breast-fed infants and infants fed trace element fortified milk-based infant formula

Infants were fed cow's milk-based formulas containing 4 mg of iron/I from 1.5 to 6 months of age and their hematological status was compared to infants receiving the same formula but with 7 mg of iron/l and with breast-fed infants. One formula with 4 mg of iron/l contained iron as ferrous sulfate, in another, part of the iron was provided as bovine lactoferrin. We also studied the effect of selenium (10 μg/l) and copper (0.4 mg/l) supplementation on selenium and copper status. There were no significant differences in hematological indices among the groups at 6 months of age; all infants had satisfactory iron status. Serum transferrin receptor levels, a potential novel indicator of iron status, were highest in breast-fed infants, suggesting a cellular need for iron, and lowest in infants receiving formula with 7 mg of iron/l. Selenium status, as assessed by serum glutathione peroxidase activity, was similar at 6 months of age in breast-fed infants and infants fed formula fortified with selenium but lower in infants fed unfortified formula. The lowest levels of glutathione peroxidase activity were found in infants fed the highest concentration of iron (7 mg/l). Serum copper concentrations were similar in all groups, but the lowest levels were found in infants fed the highest concentration of iron. These results suggest that 4 mg of iron/l is adequate for infants up to 6 months of age and that higher levels may have some negative effects.     

亚硒酸钠及维生素E治疗小儿肾病综合征远期疗效分析

目的评价亚硒酸钠及维生素E(VitE)治疗小儿肾病综合征(NS)远期疗效。方法57例NS患儿在常规使用激素的基础上,37例(NS组)服用亚硒酸钠,0.5mg／d,连服1周,以后每周0.5mg,同时服VitE,50mg／次,3次／d,疗程6个月;20例为对照组。观察两组患儿治疗前后血清硒(Se)、血浆谷胱甘肽过氧化物酶(GSH-Px)活力、丙二醛(MDA)及血清免疫球蛋白等指标,随访1.6-7.5年,观察其远期疗效。结果NS组血清Se含量及GSH-Px活力明显增加(P<0.01),MDA显著降低(P<0.05),免疫球蛋白恢复正常。完全缓解NS组33例(89.19％),对照组6例(30.00％);NS组复发3例(9.09％),对照组复发4例(66.67％)。NS组远期疗效显著优于对照组(P<0.05),复发率显著低于对照组(P<0.05)。结论用亚硒酸钠及VitE治疗NS患儿,可提高缓解率,降低复发率;Se含量减少,免疫球蛋白合成不足可能是NS容易感染引起复发的原因之一。     

Oxidant and antioxidant levels in preterm newborns with idiopathic hyperbilirubinaemia

OBJECTIVES: Newborns, particularly preterm infants, have limited antioxidant protective capacity. The organism's defence system against reactive oxygen species including vitamins A, E and C, trace element selenium (Se) and enzymes, such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) are essential components of the antioxidant system against the oxidative injury to the cellular membranes of erythrocytes. In this study, our aim was to compare the oxidant nitric oxide (total plasma nitrite level as an indicator of nitric oxide (NO)), antioxidant vitamins and selenium and erythrocyte antioxidant enzymes in premature babies with hyperbilirubinaemia with healthy preterms. METHODS: Twenty preterm infants with newborn jaundice were included in the study group, while 15 preterm infants without jaundice were enrolled in the control group. We evaluated the mean plasma levels of, respectively, the total nitrite as an indicator of NO, bilirubin, vitamins A, E, C and selenium, and the activity of erythrocyte antioxidant enzymes such as CAT, SOD and GSH-Px of preterm infants with idiopathic hyperbilirubinaemia and compared to those of the control group. RESULTS: The mean plasma total nitrite and total serum bilirubin levels and blood reticulocyte counts of the study group were found to be significantly higher than those of the control group (P < 0.001, P < 0.001 and P < 0.05, respectively). Furthermore, the activity of erythrocyte antioxidant enzymes (all P < 0.001) and the mean plasma levels of the antioxidant vitamins A, E, and C (P < 0.05, P < 0.05 and P < 0.001, respectively) and selenium (P < 0.001) of the study group were all found to be significantly lower than those of the control group. CONCLUSION: We hypothesize that low antioxidants in pretem babies may predispose them to increased oxidative stress, and cause hyperbilirubinaemia.     

Selenium requirements in patients with inborn errors of amino acid metabolism and selenium deficiency

The diets of 5 patients with phenylketonuria or maple-syrup-urine disease were supplemented with yeast which was rich in selenium. For 120 days the patients received 45 g Se/day to increase the Se content of their diets to 10–12ng Se/Kjoule. Before supplementation the selenium content of serum (5–15 ng/ml) and whole blood (10–27 ng/ml), and the activity of the erythrocyte glutathione peroxidase (0.19–2.69 U₃₇/g Hb), amounted to only 10–20% of normal. The serum selenium content reached normal values within 4 weeks of supplementation, followed by normalisation of the selenium content of whole blood within 4–8 weeks. Restoration of the activity of erythrocyte glutathione peroxidase took 9 to 15 weeks —the red cell life span. There was a significant positive correlation between the selenium content of the erythrocytes and the activity of erythrocyte glutathione peroxidase.With support of Deutsche Forschungsgemeinschaft