Low Plasma Selenium Concentrations Research Articles

Prevalence and correlates of low plasma selenium concentrations in peritoneal dialysis patients

ObjectiveSelenium is a key component in multiple enzyme systems, and dialysis patients with lower levels have been reported to have increased mortality. Low selenium levels were commonly reported in historic hemodialysis patients, but not in recent studies. There have been very few studies in peritoneal dialysis (PD) patients, and with the increasing age and frailty of our PD population we wished to review factors associated with lower selenium in PD patients. Design & methodsWe retrospectively reviewed plasma selenium, normal laboratory >0.8 umol/L, measurements from a cohort of PD patients, attending for routine peritoneal membrane assessments, along with measurement of dialysis adequacy (Kt/Vurea), and normalized nitrogen appearance rate (nPNA) and bioimpedance measured extracellular water (ECW)/total body water (TBW), and skeletal muscle mass indexed for height (SMMI). ResultsThe median plasma selenium was 0.84 (IQR-0.72–1.01) umol/L in 406 PD patients, 61.1 % male, mean age 59.0 ± 15.5 years, 44.9 % diabetic with 15.8 % designated as clinically frail (CFS). 41.4 % had selenium deficiency (<0.8 umol/L), and was more common with increasing CFS (χ2−6.8, p < 0.009), comorbidity grade(χ2−26.74, p < 0.001).Plasma selenium correlated with serum total protein (TP) (r = 0.352), albumin (r = 0.358), nPNA (r = 0.263), and negatively with ECW/TBW (r= -0.321) all p < 0.001, and positively with SMMI (rho = 0.109, p = 0.03). On multivariable analysis selenium was independently associated with TP (β 0.799 ± 0.15,95 % confidence limits (95CL) (0.505−1.093), p=<0.001), and negatively with C reactive protein (CRP) (β -0.02 ± 0.01, (95CL -0.047 to -0.005) p = 0.01), and ECW/TBW (β -1.499 ± 0.42 (95CL -2.33 to -0.666) p=<0.001). ConclusionsCompared to recent studies in hemodialysis patients, we report a 41 % prevalence for low selenium levels. Plasma selenium was positively associated with total serum protein, and negatively with CRP and ECW/TBW. Thus, lower selenium concentrations were linked to reduced dietary protein intake, and increasing frailty, inflammation and ECW/TBW ratios.

Plasma and breast-milk selenium in HIV-infected Malawian mothers are positively associated with infant selenium status but are not associated with maternal supplementation: results of the Breastfeeding, Antiretrovirals, and Nutrition study

Selenium is found in soils and is essential for human antioxidant defense and immune function. In Malawi, low soil selenium and dietary intakes coupled with low plasma selenium concentrations in HIV infection could have negative consequences for the health of HIV-infected mothers and their exclusively breastfed infants. We tested the effects of lipid-based nutrient supplements (LNS) that contained 1.3 times the Recommended Dietary Allowance of sodium selenite and antiretroviral drugs (ARV) on maternal plasma and breast-milk selenium concentrations. HIV-infected Malawian mothers in the Breastfeeding, Antiretrovirals, and Nutrition study were randomly assigned at delivery to receive: LNS, ARV, LNS and ARV, or a control. In a subsample of 526 mothers and their uninfected infants, we measured plasma and breast-milk selenium concentrations at 2 or 6 (depending on the availability of infant samples) and 24 wk postpartum. Overall, mean (± SD) maternal (range: 81.2 ± 20.4 to 86.2 ± 19.9 μg/L) and infant (55.6 ± 16.3 to 61.0 ± 15.4 μg/L) plasma selenium concentrations increased, whereas breast-milk selenium concentrations declined (14.3 ± 11.5 to 9.8 ± 7.3 μg/L) from 2 or 6 to 24 wk postpartum (all P < 0.001). Compared with the highest baseline selenium tertile, low and middle tertiles were positively associated with a change in maternal plasma or breast-milk selenium from 2 or 6 to 24 wk postpartum (both P < 0.001). With the use of linear regression, we showed that LNS that contained selenium and ARV were not associated with changes in maternal plasma and breast-milk selenium, but maternal selenium concentrations were positively associated with infant plasma selenium at 2 or 6 and 24 wk postpartum (P < 0.001) regardless of the study arm. Selenite supplementation of HIV-infected Malawian women was not associated with a change in their plasma or breast-milk selenium concentrations. Future research should examine effects of more readily incorporated forms of selenium (ie, selenomethionine) in HIV-infected breastfeeding women.

Low plasma selenium concentrations in critically ill children: the interaction effect between inflammation and selenium deficiency.

IntroductionLow plasma selenium concentrations are frequent in critically ill patients. However, whether this is due to systemic inflammation, a deficient nutritional state or both is still not clear. We aimed to determine the factors associated with low plasma selenium in critically ill children while considering the inflammatory response and nutritional status.MethodA prospective study was conducted in 173 children (median age 34 months) with systemic inflammatory response who had plasma selenium concentrations assessed 48 hours after admission and on the 5th day of ICU stay. The normal reference range was 0.58 μmol/L to 1.6 μmol/L. The outcome variable was ‘low plasma selenium’, which was defined as plasma selenium values below the distribution median during this period. The main explanatory variables were age, malnutrition, sepsis, C-reactive protein (CRP), and clinical severity scores. The data were analyzed using a Binomial Generalized Estimating Equations model, which includes the correlation between admission and 5th day responses.ResultsMalnutrition and CRP were associated with low plasma selenium. The interaction effect between these two variables was significant. When CRP values were less than or equal to 40 mg/L, malnutrition was associated with low plasma selenium levels (odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.39 to 7.63, P = 0.007; OR = 2.98, 95% CI 1.26 to 7.06, P = 0.013; OR = 2.49, 95% CI 1.01 to 6.17, P = 0.049, for CRP = 10, 20 and 40 mg/L, respectively). This effect decreased as CRP concentrations increased and there was loose significance when CRP values were >40 mg/L. Similarly, the effect of CRP on low plasma selenium was significant for well-nourished patients (OR = 1.13; 95% CI 1.06 to 1.22, P <0.001) but not for the malnourished (OR = 1.03; 95% CI 0.99 to 1.08, P = 0.16).ConclusionsThere is a significant interaction between the magnitude of the inflammatory response and malnutrition on low plasma selenium. This interaction should be considered when interpreting plasma concentrations as an index of selenium status in patients with systemic inflammation as well as in the decision on selenium supplementation.

Association of low plasma selenium concentrations with poor muscle strength in older community-dwelling adults: the InCHIANTI Study

Association of low plasma selenium concentrations with poor muscle strength in older community-dwelling adults: the InCHIANTI Study

Association of low plasma selenium concentrations with poor muscle strength in older community-dwelling adults: the InCHIANTI Study

Background: Although selenium plays an important role in muscle function, the relation between circulating selenium and muscle strength in elderly adults has not been characterized.Objective: The objective was to examine the hypothesis that low plasma selenium is associated with poor muscle strength in older adults.Design: We measured plasma selenium and hip, grip, and knee strength in a cross-sectional study of 891 men and women aged ≥65 y from the Invecchiare in Chianti (InCHIANTI) Study, a population-based cohort study in Tuscany (Italy). Poor muscle strength was defined as the lowest quartile of hip flexion, grip, and knee extension strength.Results: Overall, mean (±SD) plasma selenium was 0.95 ± 0.15 μmol/L. After adjustment for age, sex, education, total energy intake, body mass index, and chronic disease, participants in the lowest versus the highest quartile of plasma selenium were at higher risk of poor hip strength [odds ratio (OR): 1.69; 95% CI: 1.02, 2.83; P = 0.04, P for linear trend = 0.04], knee strength (OR: 1.94; 95% CI: 1.18, 3.19; P = 0.009, P for linear trend = 0.01), and grip strength (OR: 1.94; 95% CI: 1.19, 3.16; P = 0.008, P for linear trend = 0.08).Conclusions: Low plasma selenium is independently associated with poor skeletal muscle strength in community-dwelling older adults in Tuscany.

Time course and relationship between plasma selenium concentrations, systemic inflammatory response, sepsis, and multiorgan failure

Selenium plays an important role in defence against acute illness. We investigated, in intensive care unit (ICU) patients, the time course of plasma selenium concentrations and their relationship to systemic inflammatory response syndrome (SIRS), organ dysfunction/failure, infection, and ICU outcome. Plasma selenium and laboratory indices of organ dysfunction/failure, tissue inflammation, and infection were measured daily during the ICU stay in 60 consecutive ICU patients, 15 in each of four a priori defined subgroups: ICU controls (no SIRS); uncomplicated SIRS; severe SIRS; and severe sepsis/septic shock. Plasma selenium concentrations were below standard values for healthy subjects (74 microg litre(-1)) in 55 patients (92%). Selenium concentrations decreased during the ICU stay in all groups, except controls, to a minimum value that was lower in patients with organ failure, particularly in those with infection. The minimum plasma selenium was inversely correlated to admission Acute Physiology and Chronic Health Evaluation II and Simplified Acute Physiology System II scores, indicators of inflammation, and the maximal degree of organ dysfunction/failure during the ICU stay. Plasma selenium was positively correlated with minimum platelet count, minimum plasma antithrombin activity, and protein C activity. In a receiver operator characteristic analysis, SAPS II score [area under the curve (AUC) = 0.903] and minimum selenium concentration (AUC = 0.867) were the strongest predictive factors for ICU mortality. In critically ill surgical patients, plasma selenium concentrations are generally low with a greater decrease during the ICU stay in patients with organ failure, especially when attributed to infection. Lower plasma selenium concentrations are associated with more tissue damage, the presence of infection or organ dysfunction/failure, and increased ICU mortality.

Glutathione, glutathione peroxidase, and selenium status in HIV-positive and HIV-negative adolescents and young adults

Background: Antioxidant nutrient deficiencies may hasten the progression of HIV disease by impairing antioxidant defenses.Objective: The objective of the study was to determine whether HIV infection is associated with poor selenium status and low antioxidant protection by glutathione and glutathione peroxidase (GPX).Design: In a cross-sectional study of 365 HIV-positive and HIV-negative adolescents and young adults, we examined the relation of plasma selenium, whole-blood glutathione, and whole-blood GPX to HIV status, disease severity, immune activation, and oxidative damage.Results: Selenium deficiency (plasma selenium <0.070 μg/mL) was not seen in any subjects, and plasma selenium in 244 HIV-positive subjects (0.120 ± 0.0013 μg/mL) did not differ significantly (P = 0.071) from that in 121 HIV-negative subjects (0.125 ± 0.0020 μg/mL) . However, multiple regression analysis after adjustment for covariates showed a significant (P = 0.002) negative association between HIV-associated immune activation (plasma neopterin) and plasma selenium concentrations. GPX activity was highest in HIV-positive subjects taking antiretroviral therapy (median: 14.2; 25th, 75th percentiles: 11.1, 18.7 U/mL; n = 130), intermediate in HIV-positive subjects not taking antiretroviral therapy (11.8; 9.4, 15.1 U/mL; n = 114), and lowest in HIV-negative subjects (10.6; 8.6, 12.7 U/mL; n = 121; P < 0.05 for all comparisons). GPX was also positively associated with malondialdehyde, a marker of oxidative damage.Conclusions: Subjects had adequate selenium status, although HIV-related immune activation was associated with lower plasma selenium concentrations. GPX activity appears to have been induced by the oxidative stress associated with HIV infection and use of antiretroviral therapy. Thus, young, well-nourished subjects can mount a compensatory antioxidant response to HIV infection.

Low plasma selenium concentrations, high plasma human immunodeficiency virus load and high interleukin-6 concentrations are risk factors associated with anemia in adults presenting with pulmonary tuberculosis in Zomba district, Malawi

Although anemia is common among adults with pulmonary tuberculosis and human immunodeficiency virus (HIV) infection in sub-Saharan Africa, the factors contributing to its pathogenesis have not been well characterized. To characterize the antioxidant micronutrient status, interleukin-6 (IL-6) concentrations, and HIV load in relationship with anemia in adults with pulmonary tuberculosis. Zomba district, Malawi. Erythropoietin, IL-6, plasma HIV load, and markers of micronutrient status (hemoglobin (Hb), plasma concentrations of retinol, alpha-tocopherol, carotenoids, ferritin, zinc, and selenium) were measured in 500 adults who presented with pulmonary tuberculosis in Zomba Central Hospital, Malawi. Among 370 HIV-positive and 130 HIV-negative adults, the prevalence of anemia was 88 and 77%, respectively (P = 0.002), and moderate to severe anemia (Hb < 80 g/l) occurred in 30 and 15%, respectively (P = 0.001). Geometric mean IL-6 concentration was 21.1 pg/ml, with no difference between HIV-positive and -negative adults. The erythropoietin response to anemia was not different between adults with elevated IL-6 and those with lower IL-6 concentrations. In a multivariate logistic regression model, HIV load, and lower plasma selenium concentrations were associated with moderate to severe anemia. In a final multivariate linear regression model, IL-6, plasma HIV load, and plasma selenium concentrations were associated with Hb concentrations. This study suggests that low selenium concentrations, high HIV load, and high IL-6 concentrations are associated with anemia in adults with pulmonary tuberculosis in sub-Saharan Africa.

Increase in selenium requirements with physical activity loads in well‐trained athletes is not linear

Selenium requirements in athletes are supposed to be increased with energy expenditure (EE) to preserve selenium status and an optimal antioxidant balance. The question of whether selenium intakes are related to EE and whether plasma selenium status induces up-regulation in erythrocyte endogenous antioxidant defense and decreases plasma oxidative damage markers in athletes was addressed. 118 well-trained athletes completed 7 d food and activities records in a cross-sectional study. Blood was sampled on day 8. Among the athletes, 23% of the males and 66% of the females had selenium intakes below two-third of the French RDA. Plasma selenium concentrations in most of less trained athletes were lower than the postulated concentration to be required to maximize erythrocyte GSH-Px activity. Athletes with the highest daily EE had the highest selenium intakes, percentage of vegetal protein intakes and plasma selenium concentrations. Only 2.6% of the athletes exhibited low plasma selenium concentrations (< 0.75 micromol/l). The relation between plasma selenium and EE was polynomial (r = 0.50; P < 0.005). Erythrocyte GSH-Px activity in athletes was not linked to selenium status. Selenium requirements are increased in athletes without being linearly related to EE.

Dietary and Biochemical Selenium Status of Urban 6- to 24-Month-Old South Island New Zealand Children and their Postpartum Mothers

A community-based, cross-sectional survey was conducted in the South Island of New Zealand to assess the dietary and biochemical selenium status of children (n = 136) and their mothers (n = 302), and to assess factors influencing selenium status. Serum and plasma samples from children and their mothers were analyzed for selenium using graphite furnace atomic absorption spectrometry. Dietary selenium intakes were analyzed from 3-d weighed diet records, and food sources of selenium were quantified. Mean dietary selenium intakes in infants (6-11.9 mo), toddlers (12-24 mo), and mothers were below recommended levels. Toddlers had higher selenium intakes than infants (13.7 +/- 8.4 and 7.9 +/- 6.2 microg/d, respectively, P = 0.0001) and the selenium density of their diets was also higher [3.2 +/- 1.7 and 2.4 +/- 1.7 microg/(MJ . d), respectively, P = 0.003]. Household smoking was associated with lower serum selenium concentrations in infants and toddlers (P = 0.02). South Island women who were currently pregnant had lower plasma selenium concentrations (0.74 +/- 0.15 micromol/L) than nonpregnant lactating and nonpregnant nonlactating women (0.94 +/- 0.16 and 0.93 +/- 0.16 micromol/L, respectively, P = 0.0001). Clearly, pregnant women, infants and toddlers are at risk of suboptimal selenium status, and further research is warranted to assess potential effects in these groups. The finding of an association between household smoking and lower selenium concentrations in children should be investigated further. Dietary interventions are recommended to improve dietary selenium intakes in South Island children and their mothers.

An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status

Dietary selenium intakes in many countries, including the United Kingdom, are lower than international recommendations. No functional consequences of these lower intakes have been recognized, although experimental studies suggest that they might contribute to reduced immune function, increased cancer incidence, and increased susceptibility to viral disease. The objective was to assess whether administration of small selenium supplements to otherwise healthy UK subjects leads to functional changes in immune status and the rates of clearance and mutation of a picornavirus: live attenuated polio vaccine. Twenty-two adult UK subjects with relatively low plasma selenium concentrations (<1.2 micromol/L, approximately 60% of those screened) received 50 or 100 microg Se (as sodium selenite) or placebo daily for 15 wk in a double-blind study. All subjects received an oral live attenuated poliomyelitis vaccine after 6 wk and enriched stable (74)Se intravenously 3 wk later. Selenium supplementation increased plasma selenium concentrations, the body exchangeable selenium pool (measured by using (74)Se), and lymphocyte phospholipid and cytosolic glutathione peroxidase activities. Selenium supplements augmented the cellular immune response through an increased production of interferon gamma and other cytokines, an earlier peak T cell proliferation, and an increase in T helper cells. Humoral immune responses were unaffected. Selenium-supplemented subjects also showed more rapid clearance of the poliovirus, and the poliovirus reverse transcriptase-polymerase chain reaction products recovered from the feces of the supplemented subjects contained a lower number of mutations. The data indicate that these subjects had a functional selenium deficit with suboptimal immune status and a deficit in viral handling. They also suggest that the additional 100 microg Se/d may be insufficient to support optimal function.

Selenium Supplements Do Not Increase Plasma Total Homocysteine Concentrations in Men and Women

Studies in rats indicate that plasma total homocysteine (tHcy) is decreased in selenium deficiency and increases with selenium supplementation. The aim of this study was to determine the effect of selenium supplements on plasma tHcy concentrations in a population that has suboptimal selenium status. Subjects from Dunedin, New Zealand (n = 189) were randomly assigned to receive a supplement containing 200 micro g selenium or placebo for 20 wk. At baseline, 67% (n = 112) of the participants had plasma selenium concentrations < 1.2 micro mol/L, a concentration believed to be that necessary for full glutathione peroxidase (Gpx) activity. At 20 wk, plasma selenium concentration and Gpx activity increased in the selenium group by 1.2 micro mol/L [95% confidence interval (CI): 1.1, 1.3] and 5.1 nkat/g protein (3.7, 6.5), respectively, changes that were significantly greater than the changes in the placebo group (P < 0.001). At 20 wk, mean changes in plasma tHcy concentrations were 0.1 micro mol/L (95% CI: -0.4, 0.5) and -0.2 micro mol/L (-0.7, 0.3) in the supplemented and placebo groups, respectively, compared to baseline. There was no difference in the mean changes in plasma tHcy between the supplemented and placebo groups (P = 0.54). These results suggest that selenium supplementation does not influence plasma tHcy concentrations in healthy populations in developed countries, whose selenium status is characterized by lower plasma selenium concentrations.

Role of selenium depletion in the effects of dialysis on mood and behavior

Depression and behavioral problems are common in patients undergoing dialysis. Researchers have reported that serum selenium concentrations are generally lower in dialysis patients than in healthy controls. Considerable evidence suggests that selenium deprivation leads to depressed mood, and high dietary or supplementary selenium seems to improve mood. Low plasma selenium concentrations in the elderly are significantly associated with senility and cognitive decline. The author suggests that dialysis-related selenium loss may play a role in biological mechanisms of psychiatric disorders in dialysis patients.

Idiosyncratic reactions: new methods of identifying high-risk patients.

This article describes the mechanisms of idiosyncratic drug reactions (IDRs) and provides an analysis of potential methods for identifying patients at high risk for antiepileptic idiosyncratic drug reactions. IDRs may be caused by toxic metabolites, either directly or indirectly (by way of an immunologic response or a free radical-mediated process). Four methods to potentially identify patients at high risk for AED IDRs are discussed: development of an "at-risk" clinical profile for a particular AED: identification of biomarkers that measure the formation of a toxic metabolite by a previously unrecognized bioactivation pathway for a particular AED; identification of biomarkers indicating deficient detoxification abilities [e.g., deficient free radical scavenging enzyme activities or low calculated oxidative protection (COP) ratios 1 and 2]; and identification of at-risk genetic markers. Clinical profiles for patients receiving valproic acid (VPA), felbamate (FBM), and lamotrigine (LTG) and who are at risk for development of AED IDRs are presented. Patients with VPA IDRs have deficient erythrocyte glutathione peroxidase activity, low plasma selenium concentrations, low COP1 ratios, and low COP2 ratios compared with age-matched controls. Patients with FBM-associated aplastic anemia have deficient erythrocyte glutathione peroxidase, superoxide dismutase (SOD), and glutathione reductase activities compared with age-matched controls. Use of at-risk clinical profiles (for VPA, FBM, and LTG) and measurement of erythrocyte glutathione peroxidase activity, erythrocyte SOD activity, and calculation of COP1 and COP2 ratios (for VPA and FBM) are inexpensive, simple methods of identifying high-risk patients for IDRs. Research is needed to further characterize the mechanism of IDRs, to investigate the clinical utility of free radical-scavenging enzyme activity measurement and calculation of COP ratios for other AED IDRs, and to develop additional methods of identifying patients at high risk for AED IDRs.

Evaluation of selenium exposure in copper refinery workers.

Concentrations of selenium in plasma and urine and activity of glutathione peroxidase in erythrocytes were determined in workers exposed to selenium and in a control group. Plasma selenium concentrations were significantly lower in exposed workers compared to the controls. Erythrocyte glutathione peroxidase activity in selenium workers was significantly higher than in the control subjects. Urine selenium concentrations were not statistically different between the two groups. There was a significant positive correlation between plasma selenium concentrations and urine selenium concentrations in workers exposed to selenium. A weak significant positive correlation was found between plasma selenium concentrations and erythrocyte glutathione peroxidase activity in exposed workers. Our results suggest that the lower plasma selenium concentrations in selenium workers may be attributed to an increase of urinary selenium excretion.

A low plasma selenium is a risk factor for peripartum cardiomyopathy. A comparative study in Sahelian Africa

A specific selenium deficiency is a risk factor for Keshan disease, an endemic cardiomyopathy observed in China. In a Sahelian area of Niger, plasma selenium concentration was measured by neutronic activation and particle induced X-ray emission in 35 black African women with peripartum cardiomyopathy and 36 breast-feeding women without cardiac failure as controls. The plasma selenium concentration in patients was lower (48 ± 25 ng/ml, mean ± standard deviation) than in controls (77 ± 16 ng/ml) ( P < 0.0001). Moreover, 40% ( 14 35 ) patients with peripartum cardiomyopathy had very low plasma selenium concentrations, below 45 ng/ml, versus none in controls. A low plasma selenium concentration is a risk factor for the Sahelian peripartum cardiomyopathy.