Increased plasma and erythrocyte selenium concentrations but decreased erythrocyte glutathione peroxidase activity after selenium supplementation in children with Down syndrome

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 improved 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 micrograms/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 but 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 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.     

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.     

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 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 German infants fed breast milk or different formulas

At birth and at 4 months of age, selenium (Se) values of 129 term infants on three different diets were determined: 50 infants were breast fed (HM), 44 received formula based on cow's milk (F) and 35 were fed "hypoallergenic formula" (PHF) (partially hydrolysed whey protein). The Se status of a group of twins (n = 12) fed "hypoallergenic formula" was compared with the respective group of singletons. All infants had low plasma Se values during early infancy. The plasma Se of breast-fed infants remained stable (plasma Se 438 ng/ml at birth and at 4 months), whereas plasma glutathione peroxidase (GSH-Px) decreased (birth: 10729 U/l; 4 months: 6211 U/l). The formula-fed infants showed a reduction in plasma Se levels from birth to 4 months (3810 ng/ml and 299 ng/ml, respectively). The decrease was even more pronounced in infants fed the "hypoallergenic formula". This group presented the lowest Se values (plasma Se 399 ng/ml at birth; 206 ng/ml at 4 months). Renal excretion of Se was found to be lower in the formula-fed infants (F and PHF) compared with the HM group. There was a significant correlation between plasma and urinary Se (r = 0.62, p = 0.0001). Urinary Se ($uMg Se/g creatinine) appeared to be a good indicator of Se intake. Measurements of urine Se might be used as a screening method for the estimation of the Se supply. Weight and length increases in all infants were within the normal range. There were no differences between the different feeding groups. Glutathione peroxidase activity, human milk, infant formula, infant nutrition, screening method, selenium, selenium excretion, trace elements, twins
F Jochum, Department of Paediatrics, Heinrich-Heine-University, D-40225 Dusseldorf, Moorenstrafie 5a, Geb 23.12.02, Germany     

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.     

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     

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.     

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.     

Selenium status of infants on nutritional support

We investigated the selenium status of 5 infants while on nutritional support. After 4 weeks of parenteral nutrition a significant fall in plasma selenium concentrations was observed (mean +/- SD: 0.8 +/- 0.5 micrograms/dl; normal for this age: 3.6 +/- 0.9 micrograms/dl). In 1 infant the decline in selenium value occurred simultaneously with a transient rise in transaminases. A parallel but delayed decrease in red blood cell-glutathione peroxidase activity was seen in 3 patients. After reintroduction of enteral foods, the selenium levels increased progressively to and reached control values after 6 weeks, 4 and 5 months respectively in 3 patients, suggesting that the selenium requirement on TPN was not met. We consider it essential to provide longterm TPN patients with physiological amounts of selenium in order to prevent the progressive development of a deficiency state.     

Selenium Status of Infants on Nutritional Support

ABSTRACT. We investigated the selenium status of 5 infants while on nutritional support. After 4 weeks of parenteral nutrition a significant fall in plasma selenium concentrations was observed (mean ± SD: 0.8±0.5 μg/dl; normal for this age: 3.6±0.9 μg/dl). In 1 infant the decline in selenium value occurred simultaneously with a transient rise in transaminases. A parallel but delayed decrease in red blood cell-glutathione peroxidase activity was seen in 3 patients. After reintroduction of enteral foods, the selenium levels increased progressively to and reached control values after 6 weeks, 4 and 5 months respectively in 3 patients, suggesting that the selenium requirement on TPN was not met. We consider it essential to provide longterm TPN patients with physiological amounts of selenium in order to prevent the progressive development of a deficiency state.     

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     

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。     

Concentrations of Zinc, Copper, Manganese and Selenium in Blood and Urine of Patients with Prolactinoma

This study was designed to evaluate trace element metabolism in patients with prolactinoma. The mean concentrations of zinc in plasma, erythrocytes and urine, copper in plasma and erythrocytes and selenium in plasma were within normal limits before and after surgery. Urinary copper excretion was significantly lower than in controls, before surgery (<0.05) and rose towards normal after treatment. Erythrocyte manganese content was significantly lower than in controls, in patients with prolactinoma before surgery P<0.05) and rose towards normal after treatment.     

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.     

The Impact of Cardiopulmonary Bypass on Selenium Status,Thyroid Function,and Oxidative Defense in Children

Selenium has important functions for oxidative defense and thyroid hormone metabolism. Selenium-dependent enzymes include 5-iodothyronine deiodinase and glutathione peroxidase (GPX). The objective of this study was to investigate the relationship between plasma selenium, GPX activity, and thyroid hormone status in pediatric cardiac surgical patients. Plasma concentrations of selenium, free triiodothyronine (fT3), free thyroxin (fT4), and c-reactive protein as well as plasma activity of GPX were prospectively evaluated at anesthetic induction and 48 hours postoperatively in 59 children requiring cardiopulmonary bypass (CPB). GPX was measured at additional time points at 6, 12, and 24 hours postoperatively. There was a significant reduction in the plasma selenium concentration after cardiopulmonary bypass with obtained median measurements of 0.61 mol/L (induction) and 0.51 mol/L (48 hours postoperatively). The fT3/fT4 ratio decreased significantly from 0.28 at anesthetic induction to 0.22 at 48 hours postoperatively. There were no significant changes of GPX activity. 48 hours fT3 concentration, fT3/fT4 ratio, and selenium concentration were significantly negatively correlated with the time spent in intensive care. The concentration of plasma selenium in children undergoing cardiopulmonary bypass significantly decreases, resulting in diminished deiodinase activity, and a subsequent reduction in the conversion of T4 to T3.     

Selenium status of preterm infants fed human milk, preterm formula, or selenium-supplemented preterm formula

The selenium status of 46 orally fed vitamin E-sufficient preterm infants (birth weight less than 1700 gm) was studied longitudinally for 3 weeks to determine the efficacy of selenium supplementation. Infants were fed either human milk (n = 21; 24 ng selenium/ml), preterm formula (n = 13; 7.8 ng selenium/ml), or preterm formula supplemented with sodium selenite (n = 12; 34.8 ng selenium/ml). Plasma and erythrocyte selenium and glutathione peroxidase activity and urinary and dietary selenium content were evaluated on study day 1 (day enteral feeds reached 100 kcal/kg/day) and weekly for 3 weeks. Throughout the study, selenium intakes of infants fed preterm formula plus sodium selenite were greater than those of infants fed human milk, which were greater than those of infants fed preterm formula (p less than 0.001). After 3 weeks no differences were observed among groups for plasma or erythrocyte selenium or glutathione peroxidase. Plasma selenium and glutathione peroxidase values within all groups were low compared with those reported for term infants fed human milk. Whereas urinary selenium levels of infants fed preterm formula plus sodium selenite were greater than those of infants fed preterm formula at weeks 1 and 2 (p less than 0.01), infants fed human milk and preterm formula had lower levels at week 3 than on study day 1 (p less than 0.05). We conclude that blood selenium measurements typically used to monitor selenium status do not reflect dietary selenium intakes of orally fed preterm infants.