Higher Plasma Selenium Research Articles

Associations among global long interspersed nuclear element-1 DNA methylation, metal exposure, and chronic kidney disease.

Long interspersed nuclear element-1 (LINE-1) methylation serves as an indicator of global DNA methylation. This study explored the correlation between LINE-1 methylation and chronic kidney disease (CKD). We also evaluated whether LINE-1 methylation could modify the association between CKD and metal exposure. A total of 213 patients with clinically defined CKD, without hemodialysis and 416 age and sex matched controls were recruited. Levels of LINE-1 methylation, total urinary arsenic, blood lead, blood cadmium, and plasma selenium were assessed. The results reveal a positive association between LINE-1 methylation and CKD, with an odds ratio (OR) of 5.30 (95% confidence interval: 2.81 to 9.99). Total urinary arsenic and blood cadmium concentrations were positively related with LINE-1 methylation. This study was the first to observe that low plasma selenium, high blood cadmium, and high blood lead levels significantly and additively interact with increased LINE-1 methylation to increase the OR of CKD. Additionally, high LINE-1 methylation interacted multiplicatively with low plasma selenium to increase the OR of CKD (p < 0.001). This study highlighted the significant association between LINE-1 hypermethylation and CKD. Furthermore, the results demonstrate that LINE-1 methylation can interact with high blood cadmium or low plasma selenium to affect CKD risk.

Nutrition status and incidence of malnutrition in home enteral nutrition patients: A cross sectional study

Home enteral nutrition (HEN) is a long-term, life-sustaining nutrition therapy for patients unable to consume sufficient food orally. Patients rely on a prescribed, manufactured product to provide their full nutrient requirements, although some patients may have supplementary oral intake. Prescribed enteral nutrition is used as a treatment for malnutrition, but may, in the long-term, cause poor nutrition status. This study aimed to investigate the nutrition status (energy, protein, vitamin D, and selenium) and malnutrition incidence in long-term HEN patients in the Counties Manukau region. In this cross-sectional study, 42 adults on HEN for 4+ weeks under the care of Te Whatu Ora Health New Zealand were analysed. Participants’ enteral and oral feeding regimes were tracked using patient records and five non-consecutive 24-hour recalls. Biochemical markers, body mass index (BMI), body composition (BIA), and nutrition focussed physical findings were evaluated using reference standards and the Global Leadership Initiative on Malnutrition (GLIM) malnutrition criteria(1). Independent t-tests and Mann-Whitney tests compared participants based on their enteral and supplementary oral intakes and adherence to their enteral prescription. Dependent t-tests and Wilcoxon tests evaluated nutrients contributions from various feeding methods and sources. Over half (54.7%, n = 23) relied exclusively on enteral nutrition, but 60% did not achieve their full energy prescription. Compared to requirements based on the Oxford equation and 1g/kg of body weight, energy and protein intake was low in 20% of all participants, mean intake of these participants was 1,242 ± 183 kcal and 57.5 ± 13.5 g respectively. Participants with full enteral intake had a significantly higher vitamin D intake (14.9 µg, P&lt;0.05) than those with supplementary oral intake (11.2 µg, P&lt;0.05). However, those with oral intake had significantly higher intake of selenium, energy, and all the macronutrients than those with sole enteral intake. Vitamin D and selenium intakes were significantly greater in participants obtaining their full prescription than those that did not. No participants had low vitamin D or selenium blood concentrations, however 40% and 38.1% respectively were high. There was a significant relationship between meeting their energy prescription and high plasma selenium. Low BMI, mid arm muscle circumference, and fat free mass index were observed in 47.5%, 40.5%, and 44.8% of participants respectively. This was not statistically significant between groups. Fat mass and waist circumference were significantly higher in participants on full enteral nutrition. According to the GLIM malnutrition criteria, 62.5% (n = 25) of all participants were malnourished. In conclusion, while HEN patients maintain good vitamin D and selenium status, energy and protein malnutrition are evident. The types of food consumed by those with oral intake may be responsible for the differences in nutritional status. Further attention to prescription adherence and nutritional balance from HEN and oral intake is necessary for this vulnerable group.

Association of selenium profile with neutralizing antibody response to inactivated SARS-CoV-2 vaccination

BackgroundSelenium profile has been related with humoral immune response after vaccination, but evidence with regard to inactivated SARS-CoV-2 vaccine is lacking. ObjectiveThe current study aimed to examine the relationship between selenium profile and neutralizing antibody response to inactivated SARS-CoV-2 vaccine. MethodsPlasma selenium and selenoprotein P concentrations, neutralizing antibody against the wild-type and Omicron variant were measured at baseline and at 14 days, 98 days after the third dose of inactivated SARS-CoV-2 vaccine. ResultsNeutralizing antibody against the wild-type and Omicron variant increased significantly after the third vaccination dose. Both higher plasma selenium and selenoprotein P were associated with increased neutralizing antibody against the wild-type strain at baseline. Moreover, higher plasma selenoprotein P was associated with increased neutralizing antibody against Omicron variant at baseline. However, nonsignificant association were observed after the third vaccine dose. ConclusionHigher selenium profile was associated with neutralizing antibody response before the third dose of inactivated SARS-CoV-2 vaccine, but not after the third dose. Further prospective cohort studies are warranted to confirm our findings.

Blood selenium level can alleviate the nephrotoxicity of lead and cadmium in the general population of the United States: a retrospective cross section analysis of population-based nationally representative data.

The current understanding of the interplay between blood selenium, cadmium and lead levels, and chronic kidney disease (CKD) is limited. Our objective was to investigate whether elevated blood selenium levels can mitigate the nephrotoxic effects of lead and cadmium. The exposure variables examined in this study include blood selenium, cadmium, and lead levels measured by ICP-MS. The outcome of interest was CKD, defined as an estimated glomerular filtration rate (eGFR) below 60mL/min/1.73 m2. In total, 10630 participants (mean (SD) age:48.9 ± 18.4; 48.3% male) were included in this analysis. The median (IQR) of blood selenium, cadmium, and lead levels was 191 (177-207) μg/L, 0.300 (0.180-0.540) μg/L, and 0.940 (0.570-1.510) μg/dL, respectively. We observed a significant positive association between cadmium and lead levels and CKD (OR; 1.86; 95%CI: 1.31- 2.64; OR:2.23; 95%CI:1.54-3.24). However, selenium had a negative association with CKD (OR:0.096; 95%CI:0.020-0.457). Based on a reference group with a selenium concentration of ≤ 191μg/L and cadmium level of > 0.300μg/L, a significant protective factor in the CKD was seen in subjects with high plasma selenium and lower cadmium concentrations (OR:0.685; 95%CI:0.515-0.912). Then selenium concentration of ≤ 191μg/L and lead level of > 0.940μg/dL were set as a reference group, and the OR for CKD decreased among the other group (OR:0.564; 95%CI;0.417- 0.762). The subgroup analysis indicated that there were no effect modifiers. Blood selenium has the potential to mitigate the nephrotoxic effects of lead and cadmium in the general population of the United States.

Inverse Association between Serum Selenium Level and Severity of Liver Fibrosis: A Cross-Sectional Study.

Selenium has been well recognized for its important role in human health. Prior studies showed that low serum selenium was associated with various diseases, including cardiovascular disease, cancer, infertility, and cognitive decline. Recent studies demonstrated an association between selenium deficiency and liver cirrhosis. In our study, we aimed to explore the association between serum selenium levels and severity of liver fibrosis. In total, 5641 participants at an age of 12 and above, from the 2017–2018 United States National Health and Nutrition Examination Survey, were enrolled. The severity of liver fibrosis was determined by liver ultrasound transient elastography. There was a significant linear decrease in liver stiffness measurement (LSM) values in male groups with increased serum selenium levels. The beta coefficient (β) = −1.045 in male groups. A significantly negative association was also observed in the group of age ≥ 60. In addition, those in the highest quartile of serum selenium had lower LSM values (β = −0.416). This is the first study using LSM to demonstrate the correlation between selenium deficiency and severity of liver cirrhosis. Our findings suggest that a high plasma selenium concentration is negatively correlated with the severity of liver cirrhosis and there are gender and age differences.

A Functional Variant in SEPP1 Interacts With Plasma Selenium Concentrations on 3-Year Lipid Changes: A Prospective Cohort Study.

Background: Excess selenium has been related with adverse lipid levels in previous epidemiological studies. Meanwhile, a functional variant in SEPP1 (encodes selenoprotein P), namely rs7579, has been suggested to modulate lipid metabolism. However, the interactions between selenium status and rs7579 polymorphism on lipid changes remain unclear.Objective: To examine whether the associations between plasma selenium and 3-year lipid changes is modified by rs7579 polymorphism.Methods: A prospective cohort study was conducted among 1,621 individuals to examine the associations between baseline plasma selenium and 3-year lipid changes, as well as the interactions between plasma selenium and rs7579 polymorphism on lipid changes.Results: The median (interquartile range) concentration of plasma selenium was 91.68 (81.55–104.92) μg/L. Higher plasma selenium was associated with adverse 3-year lipid changes. Comparing the highest to the lowest quartiles of plasma selenium concentrations, 3-year lipid changes were elevated by 8.25% (95% CI: 1.54–14.96%) for triglycerides (P = 0.016), 5.88% (3.13–8.63%) for total cholesterol (P < 0.001), 7.37% (3.07–11.67%) for low-density lipoprotein cholesterol (P = 0.0008), 6.44% (2.66–10.21%) for non-high-density lipoprotein cholesterol (P = 0.0009), 4.99% (0.62–9.36%) for total cholesterol/high-density lipoprotein cholesterol ratio (P = 0.025), and 7.00% (1.55–12.46%) for low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (P = 0.012). In analyses stratified by rs7579 genotypes, positive associations between plasma selenium concentrations and 3-year changes in triglycerides, TC, LDL-C, non-HDL-C, TC/HDL-C ratio, and LDL-C/HDL-C ratio were observed among CC genotype carriers, but negative associations between plasma selenium and TC/HDL-C ratio, and LDL-C/HDL-C ratio were observed among TT genotype carriers.Conclusions: Our findings suggested that plasma selenium was associated with 3-year lipid changes differentially by rs7579 genotypes, and higher plasma selenium was associated with adverse lipid changes among rs7579 CC genotype carriers, but not among T allele carriers.

Plasma selenium levels and risk of new-onset diabetes in hypertensive adults

ObjectiveThe association between plasma selenium and new-onset diabetes in hypertensive adults is still unclear. We aimed to evaluate the relationship of baseline plasma selenium with new-onset diabetes and examine possible effect modifiers in a post-hoc analysis of the China Stroke Primary Prevention Trial (CSPPT). MethodsA total of 2367 hypertensive, non-diabetic patients with plasma selenium measurements at baseline were included. The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during the follow-up period, or fasting glucose (FG) ≥126.0 mg/dL at the exit visit. ResultsAt baseline, higher FG levels were found among participants with plasma selenium in quartile 4 (≥94.8 μg/L) (β, 1.64 mg/dL; 95%CI: 0.54, 2.73) compared to those in quartiles 1–3. During a median follow-up duration of 4.5 years, new-onset diabetes occurred in 270 (11.4%) participants. Graphic plot showed a positive association between baseline selenium levels and risk of new-onset diabetes. This was further confirmed by adjusted regression analyses; the odds ratios (OR) for new-onset diabetes comparing quartile 4 (≥94.8 μg/L) to quartiles 1–3 was 1.36 (95%CI: 1.01, 1.83). No clear trend was evident across quartiles 1–3. ConclusionsOur data suggest that high plasma selenium (≥94.8 μg/L) was associated with increased risk of new-onset diabetes in hypertensive patients.

The association between plasma selenium and chronic kidney disease related to lead, cadmium and arsenic exposure in a Taiwanese population.

This study aimed to determine the interaction of red blood cell cadmium and lead, total urinary arsenic, and plasma selenium in chronic kidney disease (CKD). We recruited 220 CKD patients as well as 438 gender- and age-matched controls, and we defined CKD as <60 mL/min/1.73 m2 estimated glomerular filtration rate (eGFR) for three or more consecutive months. Plasma selenium and red blood cell cadmium and lead concentrations were measured by ICP-MS. Urinary arsenic species were determined via HPLC-HG-AAS and were summed to determine the total urinary arsenic concentration. Plasma selenium was positively correlated to eGFR, and subjects with high plasma selenium levels (>243.90 μg/L) had a significantly lower odds ratio (OR) and 95% confidence interval (CI) (0.23, 0.13-0.42) for CKD compared to those with low plasma selenium levels (≤ 196.70 μg/L). High plasma selenium and low red blood cell cadmium or lead concentrations interacted to decrease the OR and 95% CI for CKD (0.12, 0.06-0.26; 0.09, 0.04-0.19). High plasma selenium and low red blood cell lead levels also interacted to increase the eGFR (20.70, 15.56-26.01 mL/min/1.73 m2). This study is the first to suggest that selenium modifies the eGFR and OR in CKD induced by environmental toxicants.

Plasma selenium influences arsenic methylation capacity and developmental delays in preschool children in Taiwan

Inefficient arsenic methylation capacity has been associated with developmental delay in preschool children. Selenium has antioxidant and anti-inflammatory properties that protect experimental animals from chemically induced neurotoxicity. The present study was designed to explore whether plasma selenium levels affects arsenic methylation capacity related to developmental delay in preschool children. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 178 children with a developmental delay and 88 children without a delay were recruited. High-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry were used to determine urinary arsenic species, including arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV). Plasma selenium levels were measured by inductively coupled plasma mass spectrometry. As results, plasma selenium concentration was significantly inversely associated with the odds ratio (OR) of developmental delay. Plasma selenium concentration was positively associated with arsenic methylation capacity [percentage of inorganic arsenic and percentage of MMAV (MMAV%) decreased, and percentage of DMAV (DMAV%) increased]. High plasma selenium concentration and high DMA% significantly and additively interacted to decrease the OR of developmental delay; the OR and 95% confidence interval were 0.40 (0.18–0.90). This is the first study to show a combined dose-response effect of plasma selenium concentration and that efficient arsenic methylation capacity decreased the OR of developmental delay in preschool children.

Prenatal exposure to selenium may protect against wheezing in children by the age of 3.

IntroductionIt has been suggested that human in utero exposure to heavy metals such as selenium can reduce the prevalence of childhood asthma and allergic diseases. However, data on this topic are scarce. The objective of the present study was to assess the putative associations between maternal selenium level during pregnancy and the risk of asthma, wheezing, allergic rhinitis, and atopic dermatitis in children from the EDEN birth cohort by the age of 1 and 3 years.MethodsPlasma selenium concentrations were measured in maternal blood during mid‐pregnancy (24–28 weeks of gestation) in 861 mothers. Cohort children were followed up from birth to 3 years using health questionnaires filled out by the parents for asthma, wheezing, allergic rhinitis, and atopic dermatitis. Maternal plasma selenium was related to the childhood outcomes by the age of 1 and 3 years.ResultsOur results showed a significant negative association between a high maternal plasma selenium level during pregnancy and the risk of wheezing in the child by the age of 1 and 3 years. However, maternal plasma selenium during pregnancy was not associated with the prevalence of asthma, allergic rhinitis or atopic dermatitis.ConclusionsThe results of this study suggest that the level of fetal exposure to maternal selenium could have an influence on the risk of wheezing in infancy and potentially on the risk of developing asthma later in life.

セレン補充によるがん予防と糖尿病発症リスク

The essential trace element selenium has long been considered to exhibit cancer-preventive, antidiabetic and insulin-mimetic properties. However, recent epidemiological studies have indicated that supranutritional selenium intake and high plasma selenium levels are not necessarily preventive against cancer, and are possible risk factors for developing type 2 diabetes mellitus. The results of the SELECT, Selenium and Vitamin E Cancer Prevention Trial, in which it is hypothesized that the supplementations with selenium and/or vitamin E decrease the prostate cancer incidence among healthy men in the U.S., showed that the supplementation did not prevent the development of prostate cancer and that the incidence of newly diagnosed type 2 diabetes mellitus increased among the selenium-supplemented participants. The Nutritional Prevention of Cancer (NPC) trial showed a decreased risk of prostate cancer among participants taking 200 μg of selenium daily for 7.7 years. However, the results of the NPC trial also showed an increased risk of type 2 diabetes mellitus in the participants with plasma selenium levels in the top tertile at the start of the study. Recently, the association of serum selenium with adipocytokines, such as TNF-α, VCAM-1, leptin, FABP-4, and MCP-1, has been observed. Selenoprotein P has been reported to associated with adiponectin, which suggests new roles of selenoprotein P in cellular energy metabolism, possibly leading to the increased risk of type 2 diabetes mellitus and also the development of cancer. Further studies are required to elucidate the relationship between selenium and adipocytokines and the role of selenoprotein P in the development of type 2 diabetes mellitus and cancer at high levels of selenium.

Influence of the glutathione peroxidase 1 Pro200Leu polymorphism on the response of glutathione peroxidase activity to selenium supplementation: a randomized controlled trial

A genetic variant at codon 200 (Pro200Leu) of the gene encoding for glutathione peroxidase 1 (GPx1), a selenium-dependent enzyme, is associated with lower enzyme activity; however, the evidence is limited to in vitro and observational studies. The objective was to determine whether the GPx1 Pro200Leu genetic variants modify the response of whole-blood glutathione peroxidase (GPx) activity to selenium supplementation in patients with coronary artery disease in New Zealand. The results from 2 parallel-design, double-blind trials were combined. Participants were randomly assigned to receive a daily supplement of 100 μg Se as l-selenomethionine (n = 129) or placebo (n = 126) for 12 wk. Plasma selenium and whole-blood GPx activity were measured at baseline and at week 12. Participants were genotyped for the GPx1 Pro200Leu polymorphism. Selenium supplementation increased whole-blood GPx activity by 5 (95% CI: 4, 7) U/g hemoglobin (P < 0.001); however, the magnitude of the increase did not differ by genotype (P = 0.165 for treatment-by-genotype interaction). In an exploratory analysis, a significant nutrient-gene interaction was apparent when baseline plasma selenium concentrations were included in the regression model (P = 0.006 for treatment-by-genotype × baseline selenium concentration interaction). Increases in GPx activity were 2-fold higher in Pro homozygotes than in participants carrying a Leu allele when baseline selenium concentrations were ≤1.15 μmol/L (P < 0.05). These results indicate that GPx1 Pro200Leu variants do not substantially modify the response of whole-blood GPx to selenium supplementation in individuals with relatively high plasma selenium concentrations. A nutrient-gene interaction was observed when the baseline selenium concentration was low, but this requires independent confirmation. This trial was registered at www.actr.org.au as ACTRN12605000412639 and ACTRN12606000197538.

Preparation and characterisation of selenium-enriched mushroom aqueous enzymatic extracts (MAEE) obtained from the white button mushroom (Agaricus bisporus)

Abstract Selenium-enriched mushroom aqueous enzymatic extracts (MAEE) were obtained from the white button mushroom (Agaricus bisporus) by a procedure based on enzyme and membrane technology. MAEE, with a selenium concentration of 51.8 ± 5.58 μg/g is a product suitable for achieving the recommended daily dose (RDD) of 55 μg with a small amount of around 1 g of product, which can be incorporated into any type of solid or liquid food without modifying its organoleptic properties. Chemical characterisation and selenium speciation are also reported; more than 86% of the selenium-containing products are organic in nature. The utilisation of this product would help in the treatment and/or prevention of diseases associated with low selenium concentrations, such as ageing, and neurodegenerative, cardiovascular and immunological diseases, while avoiding the risk of reaching high plasma selenium concentrations which has recently been associated with deleterious effects.

Genetic variants in antioxidant genes, Gleason grade, and prostate cancer recurrence after radical prostatectomy.

33 Background: Laboratory and genomic data suggest that the antioxidant defense system is important in prostate carcinogenesis, and that this relation may vary by plasma antioxidant status. Methods: Among 567 radical prostatectomy (RP) patients with non-metastatic prostate cancer (CaP), we examined genetic variants in SOD1(5 SNPs), SOD2(6), SOD3(6), TXRND1(5), TXRND2(21), GPX1(3), GPX3(8), GPX4(5), CAT(9), XRCC1(2), SELENBP1(5), SEP15(4), SEPP1(4), SEC14L2(8), and TTPA(4) and risk of high pathologic Gleason sum (8+ or 7 with primary 4+) using logistic regression, and CaP recurrence (PSA rise, second treatment, metastasis) using Cox proportional hazards regression. We also examined whether the genetic variants interacted with plasma selenium, alpha-tocopherol, or gamma-tocopherol in relation to risk of high grade CaP. Results: 21% (n = 117) of men had high grade CaP, and 47 recurrences occurred (median follow-up of all participants = 3 y). Men with 1+ of the less common allele (CT or TT) in rs4880 (SOD2) had a 49% reduced rate of recurrence (hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.28, 0.92), independent of grade, stage, and PSA. In contrast, men with 1+ of the less common allele in 3 of the TXRND1, 4 of the TXRND2, and 1 of the SEP15 SNPs had 2-fold increased rate of recurrence (HRs: 1.93-2.95; p-values: 0.002-0.04), and men with 2 of the less common allele in 2 of the GPX3 SNPs had 3-fold increased rate of recurrence (p-values from additive models: &lt;0.01). For high grade CaP, men with 1+ of the less common allele in 1 of the SOD3 SNPs or 2 of the less common alleles in 2 of the TXRND2 SNPs had 2-fold increased risk (p-values = 0.007-0.02), while men with 1+ of the less common allele in 1 of the GPX1 SNPs had 37% reduced risk (p-value = 0.04). Among men with certain genotypes in 3 TXRND2, 1 GPX3, or 2 CAT SNPs, high plasma selenium reduced risk of high grade CaP by 50-76%. Among men with certain genotypes in 1 SOD1 or 1 SOD2 SNP, high plasma alpha-tocopherol reduced risk of high grade CaP by 65-68%. Conclusions: Genetic variants in antioxidant genes may be associated with CaP recurrence after RP, and may interact with plasma selenium and alpha-tocopherol in relation to risk of high grade CaP.

A Balanced Diet?: Selenium May Offset the Effects of Methylmercury on Cataract Development

Dietary exposure to mercury from fish has been posited as a risk factor for cataracts because some reports have suggested methylmercury accumulates in the lens of the eye. But selenium from other dietary sources may offset that damage, according to a study of communities in the Amazon basin [EHP 118(11):1584–1589; Lemire et al.]. The findings, while preliminary, hint at potential public health measures in areas where methylmercury-contaminated fish are a significant part of people’s diets. With old age comes cataracts, particularly in latitudes like the Amazon, where higher ultraviolet radiation exposure and other environmental factors contribute to the clouding of the lenses in human eyes. And while surgical fixes exist for cataracts, people in isolated regions may not always have access to those options. Cataracts therefore are a major cause of blindness among older people in the Amazon. The current study involved communities that eat fish from the Tapajos River, a tributary of the Amazon. People here have among the highest reported exposures to mercury in the world. Deforestation in the region leads to the release of natural inorganic mercury from soils into surface waters, where it is methylated and eventually ends up in fish. Several hundred people voluntarily participated in the study, which entailed taking an overnight boat trip to a nearby city where participants gave blood samples and were examined by optometrists. In the end, 211 people over age 40 were included in the analysis. A third of them had age-related cataracts. Low plasma selenium and high blood mercury each were associated with a higher prevalence of cataracts (over 2 and 4 times higher, respectively). The team calculated that the people with both low plasma selenium and high blood mercury were 16 times more likely to develop cataracts than the “optimum situation” group, which had both high plasma selenium and low blood mercury. This is the first study known to associate high levels of methylmercury from fish consumption with increased occurrence of cataracts. The authors emphasize that other factors—such as differences in dietary intakes of antioxidants and vitamins—could confound their findings. Still, if the observed associations hold true in broader studies, public health interventions to alleviate cataracts in this Amazonian population must consider both the health benefits of fish consumption and the risks of the main source of dietary selenium in the region: brazil nuts, which also contain barium and strontium, heavy metals with their own hazards.

Higher Selenium Status is Associated with Adverse Blood Lipid Profile in British Adults1–3

Recent findings have raised concern about possible associations of high selenium exposure with diabetes and hyperlipidemia in the US, a population with high selenium status. In the UK, a population with lower selenium status, there is little data on the association of selenium status with cardio-metabolic risk factors in the general population. We examined the association of plasma selenium concentration with blood lipids in a nationally representative sample of British adults. A cross-sectional study was conducted among 1042 white participants (aged 19–64 y) in the 2000–2001 UK National Diet and Nutrition Survey. Plasma selenium was measured by inductively coupled-plasma mass spectrometry. Total and HDL cholesterol were measured in nonfasting plasma samples. Mean plasma selenium concentration was 1.10 ± 0.19 μmol/L. The multivariate adjusted differences between the highest (≥1.20 μmol/L) and lowest (<0.98 μmol/L) quartiles of plasma selenium were 0.39 (95% CI 0.18, 0.60) mmol/L for total cholesterol, 0.38 (0.17, 0.59) for non-HDL cholesterol, and 0.01 (−0.05, 0.07) for HDL cholesterol. Higher plasma selenium (i.e., ≥1.20 μmol/L) was associated with increased total and non-HDL cholesterol levels but not with HDL in the UK adult population. These findings raise additional concern about potential adverse cardio-metabolic effects of high selenium status. Randomized and mechanistic evidence is necessary to assess causality and to evaluate the impact of this association on cardiovascular risk.

High selenium intake and increased diabetes risk: experimental evidence for interplay between selenium and carbohydrate metabolism

The essential trace element selenium has long been considered to exhibit anti-diabetic and insulin-mimetic properties, but recent epidemiological studies indicated supranutritional selenium intake and high plasma selenium levels as possible risk factors for development of type 2 diabetes, pointing to adverse effects of selenium on carbohydrate metabolism in humans. However, increased plasma selenium levels might be both a consequence and a cause of diabetes. We summarize current evidence for an interference of selenium compounds with insulin-regulated molecular pathways, most notably the phosphoinositide-3-kinase/protein kinase B signaling cascade, which may underlie some of the pro- and anti-diabetic actions of selenium. Furthermore, we discuss reports of hyperinsulinemia, hyperglycemia and insulin resistance in mice overexpressing the selenoenzyme glutathione peroxidase 1. The peroxisomal proliferator-activated receptor gamma coactivator 1α represents a key regulator for biosynthesis of the physiological selenium transporter, selenoprotein P, as well as for hepatic gluconeogenesis. As proliferator-activated receptor gamma coactivator 1α has been shown to be up-regulated in livers of diabetic animals and to promote insulin resistance, we hypothesize that dysregulated pathways in carbohydrate metabolism and a disturbance of selenium homeostasis are linked via proliferator-activated receptor gamma coactivator 1α.

Selenium, Genetic Variation, and Prostate Cancer Risk: Epidemiology Reflects Back on Selenium and Vitamin E Cancer Prevention Trial

The randomized, controlled Selenium and Vitamin E Cancer Prevention Trial (SELECT) found that selenium supplementation did not decrease the risk of prostate cancer, which contradicted a secondary finding from the Nutritional Prevention of Cancer (NPC) Study. In the wake of SELECT, we expect that many groups will report results from epidemiologic studies on selenium and prostate cancer, some of which may illuminate reasons for SELECT’s null results. One such effort is reported in this issue of Journal of Clinical Oncology by Chan et al, who conducted a cross-sectional epidemiologic study of plasma selenium, an SOD2 variant, and aggressive prostate cancer in men diagnosed with clinically localized or locally advanced prostate cancer and who provided a blood specimen. They observed an unexpected positive association between plasma selenium and aggressive disease. As expected, an SOD2 variant, a substitution of alanine for valine at amino acid 16 in the antioxidant enzyme manganese superoxide dismutase, was not statistically significantly associated with aggressive disease, although the relative risks (RRs) for one or two alanine alleles were above 1.0. Two patterns emerged in the analysis of the joint association of plasma selenium and SOD2: men with low selenium and two alanine alleles had a higher risk of aggressive disease (compared with low selenium and none or one alanine alleles); high selenium seemingly protected men with two alanine alleles; and men with high selenium and none or one alanine allele had a higher risk of aggressive disease (compared with low selenium and none or one alanine allele). In light of these findings, Chan et al commented that their data “indicate caution against broad use of selenium supplementation for men with prostate cancer” and that “complete interpretation of results from SELECT may depend on assessment of SOD2 genotype in trial participants.” Before discussing the broader context (related observational studies, the NPC study, and SELECT) and implications of this study, we will discuss a design feature that complicates drawing etiologic inferences—and thus implications for selenium supplementation— from the Chan et al study. They estimated the prevalence of aggressive disease in a cohort of men with prostate cancer, making the denominator for risk calculation men with prostate cancer. Etiologic research on aggressive prostate cancer typically estimates risk of aggressive disease in a cohort of men who do not have a diagnosis of prostate cancer at baseline, making at-risk men without prostate cancer the denominator. Table 1 illustrates several hypothetical scenarios (a subset of all possible scenarios) that could explain the higher risk of aggressive prostate cancer found by Chan et al in men with higher plasma selenium. Columns 4 to 6 involve a typical cohort of at-risk men. The cohort of cancer patients (aggressive and nonaggressive) involved in column 7 is derived from the at-risk cohort and reflects the design of Chan et al. Although all are hypothetical, the data and assumptions in Table 1 are consistent with the epidemiologic literature on nutrients and genetic variants and are not out of line with the data of Chan et al (the same can be said of the hypothetical data and assumptions in Table 2, which is discussed below). Scenario D is a plausible scenario in which the increased RR of aggressive disease (1.25) in a design similar to that of the study by Chan et al would be misleading because the true RR of aggressive disease is 0.75, as illustrated by the more informative typical cohort design. Scenarios A to D are all plausible but unknowable because of this study’s design. Differences in implication make it absolutely critical to discern the correct scenario behind the Chan et al results. The implication of hypothetical scenarios A and C—caution against taking a selenium supplement—is diametrically opposed to that of B and D—a recommendation for taking a selenium supplement. The typical cohort design for etiologic research, using at-risk individuals, enables correct implications that are not derivable from a design using cancer patients at baseline. The design of the study by Chan et al is frequently used in clinical studies of potential biomarker associations or correlations with cancer aggressiveness, where inferences are unambiguous (barring other sources of error). This design also sometimes is used for etiologic research, but investigators should be alert to the etiologic ambiguity it raises for interpreting a positive or inverse association between an exposure and aggressive disease. Previously published studies in at-risk men may help in drawing inferences from the Chan et al findings on the main effects of selenium and SOD2 and their joint effects, which are even more challenging to interpret with a cohort of only cancer patients. Regarding associations between circulating selenium and overall prostate cancer, JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 27 NUMBER 22 AUGUST 1 2009

Plasma selenium concentrations in a Sikh population in Sydney, Australia.

Selenium is essential for humans because it protects the heart against cardiomyopathy. It may also reduce ischaemic heart disease owing to its antioxidant activity. It is known that Indian migrants in a number of countries have high incidences of ischaemic heart disease. In this study, fasting plasma selenium concentrations of Sikh migrants in Sydney (Australia) were measured to investigate whether selenium concentration is reduced in this community. The mean concentration of selenium in plasma (91.8 +/- 15.0 ng ml-1, n = 196) was within the normal range. A significantly higher plasma selenium concentration was demonstrated in males than in females (p < 0.01). This was mainly due to the difference in mean selenium concentrations between genders in vegetarians because no significant difference was observed in non-vegetarian males versus females. The mean concentration of selenium in teetotal males was similar to those who consumed alcohol. Despite significant variations with gender and diet, the selenium concentrations were within the normal range. The results suggest that selenium status is adequate in the Sikh community even though vegetarian diet is common and alcohol use is condones in males.

Selenium status in females with occupational cervico-brachial complaints.

A hypothesis that selenium deficiency predisposes the development of occupational cervicobrachial complaints was tested in 134 females working in an assembly factory, with constrained work postures and repetitive work tasks. Seventeen subjects, who reported intake of selenium tablets, had higher plasma selenium levels than the others (104 vs 89 micrograms/l, P = 0.01). Among those who did not take selenium tablets, 21% reported symptoms from the upper back during the last 7d, 21% from the neck, 38% from the shoulders, 15% from the elbows, and 27% from the hands. Subjects with pain in their elbows had slightly, but significantly, lower plasma selenium levels than asymptomatics (84 vs 90 micrograms/l, P = 0.048). For the other anatomical regions, there were no statistically significant differences. Thus, there was no major association between selenium status and pain; conclusions regarding any minor association must await further studies.