Exploring the association of metal mixture in blood to the kidney function and tumor necrosis factor alpha using machine learning methods.

This research aimed to approach relationships between metal mixture in blood and kidney function, tumor necrosis factor alpha (TNF-α) by machine learning. Metals levels were measured by Inductively Couple Plasma Mass Spectrometry in blood from 421 participants. We applied K Nearest Neighbor (KNN), Naive Bayes classifier (NB), Support Vector Machines (SVM), random forest (RF), Gradient Boosting Decision Tree (GBDT), Categorical boosting (CatBoost), eXtreme Gradient Boosting (XGBoost), Whale Optimization-based XGBoost (WXGBoost) to identify the effect of plasma metals, TNF-α, and estimated glomerular filtration rate (eGFR by CKD-EPI equation). We conducted not only toxic metals, lead (Pb), arsenic (As), cadmium (Cd) but also included trace essential metals, selenium (Se), copper (Cu), zinc (Zn), cobalt (Co), to predict the interaction of TNF-α, TNF-α/white blood count, and eGFR. The high average TNF-α level group was observed among subjects with higher Pb, As, Cd, Cu, and Zn levels in blood. No associations were shown between the low and high TNF-α level group in blood Se and Co levels. Those with lower eGFR group had high Pb, As, Cd, Co, Cu, and Zn levels. The crucial predictor of TNF-α level in metals was blood Pb, and then Cd, As, Cu, Se, Zn and Co. The machine learning revealed that As was the major role among predictors of eGFR after feature selection. The levels of kidney function and TNF-α were modified by co-exposure metals. We were able to acquire highest accuracy of over 85% in the multi-metals exposure model. The higher Pb and Zn levels had strongest interaction with declined eGFR. In addition, As and Cd had synergistic with prediction model of TNF-α. We explored the potential of machine learning approaches for predicting health outcomes with multi-metal exposure. XGBoost model added SHAP could give an explicit explanation of individualized and precision risk prediction and insight of the interaction of key features in the multi-metal exposure.

[Plasma selenium level and its influencing factors in Chinese child-bearing-aged women in 2015].

OBJECTIVE: To assess the plasma selenium(Se) level of child-bearing-aged women and discuss the influence factor for low-Se level. METHODS: Using the muti-stage stratified and population proportional cluster random sampling method, 1881 child-bearing-aged women aged 18 to 44 years were selected from China Adult Chronic Disease and Nutrition Surveillance(2015) Data. The basic information of the subjects was collected by unified electronic questionnaires and equipments were used for field survey, measurement and record. Plasma Se concentration was detected by inductively coupled plasma mass spectrometry. Plasma low-Se level were assessed using lower limit of plasma/serum Se established by the Mayo Clinic Laboratory and our laboratory, respectively. Influence factors of low-Se level were analyzed by the multivariate logistic regression model. RESULTS: The M(P25, P75) plasma Se concentration for Chinese child-bearing-aged women was 89.52(74.21, 105.03)µg/L. Nationality, location, urban-rural type and education level difference had influence on plasma Se level in this population(P<0.05). According to the lower limit of plasma/serum Se concentration established by the Mayo clinical laboratories(<70 µg/L) and our laboratories(<73.81 µg/L), the low-Se rate were 20.47% and 24.51%, respectively. There were significantly differences in low-Se rate among nationality, location, urban-rural type, education level and marital status(P<0.05). The multivariate logistic regression model showed that location and urban-rural type had significant effects on low-Se rate of child-bearing-aged women(P<0.05). CONCLUSION: The plasma low-Se rate of Chinese women of childbearing age is relatively high and higher prevalence low-Se was found in western and central regions and rural areas in China.

Population status of selenium in Colombia and associated factors: a cross-sectional study.

OBJECTIVES: This study aims to investigate the population status of selenium in Colombia and other associated factors. METHODS: Cross-sectional study, in population of urban or rural origin (n=412). Main outcome measures were: median serum selenium, thyrotropin, the prevalence of and positivity of anti-thyroid peroxidase, anti-thyroglobulin, and anti-TSH receptor. RESULTS: This study found that 96.6% of the subjects had normal selenium levels, and no significant associations were found between the population median of selenium and overweight/obesity, sociodemographic variables, age, goiter, and thyroid antibody positivity. CONCLUSIONS: In Colombia, the population status of selenium is normal, and the geological characteristics may contribute to the state of selenium in this population. However, additional studies are required to evaluate the content of selenium in plants and other foods.

Correlations of selenium and selenoprotein P with asymmetric dimethylarginine and lipid profile in patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with an increased risk of cardiovascular diseases (CVD). Accumulating evidence has suggested that selenium (Se) is of importance for optimal function of the cardiovascular system. This study aimed to investigate the associations of selenium and selenoprotein P (SePP) with asymmetric dimethylarginine (ADMA) and lipid profile in women with PCOS. METHODS: In this cross-sectional study, 125 females aged 18-45 years diagnosed with PCOS were recruited. An interviewer-administered questionnaire was applied to gather the relevant demographic characteristics, detailed clinical information, and lifestyle habits of participants. Fasting blood samples were obtained to measure biochemical parameters. Serum concentrations of total testosterone, sex hormone-binding globulin (SHBG), ADMA, and lipid profiles as well as anthropometric measurements were assessed across tertiles of serum Se and SePP concentrations. RESULTS: There was a positive correlation between serum Se and SePP concentrations (r = 0.434, p < 0.001). Serum Se level was inversely correlated with ADMA (r = -0.21, p = 0.025) and TG (r = -0.17, p = 0.041) concentrations. There were also inverse correlations between SePP and ADMA (r = -0.34, p < 0.001), TG (r = -0.21, p = 0.019), and oxidized low density lipoprotein (ox-LDL) (r = -0.25, p = 0.007) levels. No significant relationship was found between serum Se and SePP concentrations with total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein-A1 (Apo-A1), apolipoprotein-B (Apo-B100), total testosterone, SHBG, and free androgen index as well as anthropometric parameters (All p > 0.05). CONCLUSION: The present study found that Se and SePP levels were inversely correlated with ADMA and TG concentrations as well as ox-LDL levels.

Gestational thyroid hormone concentrations and risk of attention-deficit hyperactivity disorder in the Norwegian Mother, Father and Child Cohort Study.

BACKGROUND: Maternal thyroid function plays an important role in foetal brain development; however, little consensus exists regarding the relationship between normal variability in thyroid hormones and common neurodevelopmental disorders, such as attention-deficit hyperactivity disorder (ADHD). OBJECTIVE: We sought to examine the association between mid-pregnancy maternal thyroid function and risk of clinically diagnosed ADHD in offspring. METHODS: We conducted a nested case-control study in the Norwegian Mother, Father and Child Cohort Study. Among children born 2003 or later, we randomly sampled singleton ADHD cases obtained through linkage with the Norwegian Patient Registry (n = 298) and 554 controls. Concentrations of maternal triiodothyronine (T3), thyroxine (T4), T3-Uptake, thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (TPO-Ab) were measured in maternal plasma, collected at approximately 17 weeks' gestation. Indices of free T4 (FT4i) and free T3 (FT3i) were calculated. We used multivariable adjusted logistic regression to calculate odds ratios and accounted for missing covariate data using multiple imputation. We used restricted cubic splines to assess non-linear trends and provide flexible representations. We examined effect measure modification by dietary iodine and selenium intake. In sensitivity analyses, we excluded women with clinically significant thyroid disorders (n = 73). RESULTS: High maternal T3 was associated with increased risk of ADHD (5th vs 1st quintile odds ratio  2.27, 95% confidence interval 1.21, 4.26). For FT4i, both the lowest and highest quintiles were associated with an approximate 1.6-fold increase in risk of ADHD, with similar trends found for T4. The FT4i association was modified by dietary iodine intake such that the highest risk strata were confined to the low intake group. CONCLUSIONS: Both high and low concentrations of maternal thyroid hormones, although within population reference ranges, increase the risk of ADHD in offspring. Increased susceptibility may be found among women with low dietary intake of iodine and selenium.

Evaluation of Serum Selenium and Copper Levels with Inflammatory Cytokines and Indices of Oxidative Stress in Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is a metabolic and multifactorial disease in which inflammatory markers, oxidative stress, and certain trace elements seem to have an essential role. This study investigated the relationship between serum selenium and copper level with inflammatory cytokines and oxidative stress in T2DM.In this case-control study, 30 patients with T2DM and 30 healthy individuals were selected. Serum levels of copper and selenium were measured by atomic absorption spectrometry, and TNF-α and IL-6 and oxidative stress markers were measured by ELISA. The SPSS v.22 was used for data analysis and the significance level is less than 5%.The mean age of patients was 52.9 ± 10.4 years, and the control group was 48.5 ± 10.4 years. In this study, 53.3% were female, and 46.7% were male. The levels of BMI (p = 0.002), systolic pressure (p = 0.034), insulin, selenium, malondialdehyde, and glutathione peroxidase (p = 0.0001; each), insulin resistance, copper, and superoxide dismutase, IL6, and TNF-α (p = 0.001; each) in T2DM were significantly higher than the control group. While levels of lipid profile, uric acid, creatinine, and diastolic pressure were not significantly different between the two groups. Selenium and copper are related to insulin resistance, and their increasing levels are associated with increased levels of markers of oxidative stress and inflammatory cytokines (p < 0.05).Increased levels of copper and selenium are associated with T2DM and this increase is also associated with increased levels of TNF-α, IL-6, and oxidative stress in T2DM. Therefore, controlling these markers can lead us to control this disease better.

Blood cadmium, lead, manganese, mercury, and selenium levels in American Indian populations: The Strong Heart Study.

BACKGROUND: Many American Indian (AI) communities are in areas affected by environmental contamination, such as toxic metals. However, studies assessing exposures in AI communities are limited. We measured blood metals in AI communities to assess historical exposure and identify participant characteristics associated with these levels in the Strong Heart Study (SHS) cohort. METHOD: Archived blood specimens collected from participants (n = 2014, all participants were 50 years of age and older) in Arizona, Oklahoma, and North and South Dakota during SHS Phase-III (1998-1999) were analyzed for cadmium, lead, manganese, mercury, and selenium using inductively coupled plasma triple quadrupole mass spectrometry. We conducted descriptive analyses for the entire cohort and stratified by selected subgroups, including selected demographics, health behaviors, income, waist circumference, and body mass index. Bivariate associations were conducted to examine associations between blood metal levels and selected socio-demographic and behavioral covariates. Finally, multivariate regression models were used to assess the best model fit that predicted blood metal levels. FINDINGS: All elements were detected in 100% of study participants, with the exception of mercury (detected in 73% of participants). The SHS population had higher levels of blood cadmium and manganese than the general U.S. population 50 years and older. The median blood mercury in the SHS cohort was at about 30% of the U.S. reference population, potentially due to low fish consumption. Participants in North Dakota and South Dakota had the highest blood cadmium, lead, manganese, and selenium, and the lowest total mercury levels, even after adjusting for covariates. In addition, each of the blood metals was associated with selected demographic, behavioral, income, and/or weight-related factors in multivariate models. These findings will help guide the tribes to develop education, outreach, and strategies to reduce harmful exposures and increase beneficial nutrient intake in these AI communities.

Serum BDNF and Selenium Levels in Elite Athletes Exposed to Blows.

Background and Objectives: The study aimed to investigate the combined acute and long-term effects of exposure to blows and exercise on serum BDNF (brain-derived neurotrophic factor) and selenium levels. Materials and Methods: Serum BDNF and selenium levels were determined in 40 male elite athletes before and after vigorous exercise (training match) with a probability of exposure to blows and in 10 sedentary men subjected to exercise (Astrand running protocol). Results: Serum BDNF levels were found 11.50 ± 3.50 ng/mL before exercise and 14.02 ± 3.15 ng/mL after exercise in the athlete group (p = 0.02), and 12.18 ± 4.55 ng/ mL and 11.74 ± 2.48 ng/ mL before and after exercise in the sedentary group, respectively (p = 0.873). Serum BDNF (pre-exercise, baseline) levels were slightly lower in the athlete group than those in the sedentary group (11.50 ± 3.50 and 12.18 ± 4.55 ng/mL, respectively, p = 0.796). Pre-exercise serum selenium levels in athletes were significantly higher compared to those of sedentary participants (130.53 ± 36.79 and 95.51 ± 20.57 µg/L, respectively, p = 0.011). There was no difference in selenium levels after exercise (124.01 ± 29.96 µg/L) compared to pre-exercise (130.53 ± 36.79 µg/L) in the athlete group (p = 0.386). Similarly, there was no difference in selenium levels after exercise (113.28 ± 25.51 µg/L) compared to pre-exercise (95.51 ± 20.57 µg/L) in the sedentary group (p = 0.251). Conclusions: BDNF results show that even if athletes are exposed to blows, they may be protected from the long-term effects of blows thanks to the protective effect of their non-sedentary lifestyle. Regular exercise may have a protective effect on maintaining serum selenium levels in athletes even exposed to blows chronically.

Plasma Concentrations of Trace Elements Selenium and Cobalt During and After Coronary Artery Bypass Grafting Surgery.

Trace elements selenium (Se) and cobalt (Co) are essential in the human body, and a correlation between Se and cardiac surgery has been suggested. We investigated the plasma concentrations of Se and Co during and after coronary artery bypass grafting (CABG) surgery under cardiopulmonary bypass (CPB). From December 2019 to January 2020, preoperative plasma samples from isolated first-time CABG patients (n=20; 10 males, 10 females) were prospectively collected post-anesthesia and before CPB (T1), 45 min after CPB started (T2), 90 min after CPB started (T3), and postoperative days 1 (T4), and day 4 (T5). The plasma concentrations of Se and Co were measured. The Se concentration was significantly decreased at T2 (105.24±4.08 vs. 68.56±2.42 µg/L, p<0.001) and T3 (105.24±4.08 vs. 80.41±3.40 µg/L, p<0.001). The Co concentration was significantly decreased at T4 (0.35±0.19 vs. 0.26±0.13 µg/L, p<0.01) and T5 (0.35±0.19 vs. 0.23±0.11 µg/L, p<0.001). Five patients developed atrial fibrillation (AF); there was no other operative mortality or major morbidity. This is the first report of alterations of plasma Se and Co concentrations during and after CABG surgery. Our results may indicate that Se supplementation before or during CABG and Co supplementation after CABG may become necessary for patients undergoing CABG.

The role of selenium in depression: a systematic review and meta-analysis of human observational and interventional studies.

The results of human studies are inconsistent regarding selenium and depressive disorders. Therefore, we aimed to conduct a systematic review and meta-analysis of observational and interventional studies and provided an overview of the role of selenium in depression. Three databases including Medline, Scopus, and Web of Science were searched on June 30, 2020 and updated on April 12, 2021. Also, we searched in electronical databases of WHO Global Index Medicus and ClinicalTrials.gov. No time or language restrictions were used for the search. A random effects model was used to pool effect sizes. In total, 20 studies were included in the systematic review, and 15 studies were included in the meta-analysis. There were no significant differences in serum selenium levels between patients with depression and healthy subjects (WMD: 2.12 mg/L; 95% CI: - 0.11, 4.36; I2 = 98.0%, P < 0.001). Also, no significant correlation was found between serum levels of selenium and depression scores (r: - 0.12; 95% CI: - 0.33, 0.08; I2 = 73.5%, P = 0.010). Nevertheless, there was a significant negative association between high selenium intake and the risk of postpartum depression (OR: 0.97; 95% CI: 0.95, 0.99; I2 = 0.0%, P = 0.507). In addition, selenium supplementation significantly reduced depressive symptoms (WMD: - 0.37; 95% CI: - 0.56, - 0.18; I2 = 0.0%, P = 0.959). Taken these results together, selenium seems to have a protective role against postpartum depression and can be considered as a beneficial adjuvant therapy in patients with depression. Further studies are necessary to draw definitive conclusions.

The Effect of Circulating Zinc, Selenium, Copper and Vitamin K1 on COVID-19 Outcomes: A Mendelian Randomization Study.

Background & Aims: Previous results from observational, interventional studies and in vitro experiments suggest that certain micronutrients possess anti-viral and immunomodulatory activities. In particular, it has been hypothesized that zinc, selenium, copper and vitamin K1 have strong potential for prophylaxis and treatment of COVID-19. We aimed to test whether genetically predicted Zn, Se, Cu or vitamin K1 levels have a causal effect on COVID-19 related outcomes, including risk of infection, hospitalization and critical illness. Methods: We employed a two-sample Mendelian Randomization (MR) analysis. Our genetic variants derived from European-ancestry GWAS reflected circulating levels of Zn, Cu, Se in red blood cells as well as Se and vitamin K1 in serum/plasma. For the COVID-19 outcome GWAS, we used infection, hospitalization or critical illness. Our inverse-variance weighted (IVW) MR analysis was complemented by sensitivity analyses including a more liberal selection of variants at a genome-wide sub-significant threshold, MR-Egger and weighted median/mode tests. Results: Circulating micronutrient levels show limited evidence of association with COVID-19 infection, with the odds ratio [OR] ranging from 0.97 (95% CI: 0.87-1.08, p-value = 0.55) for zinc to 1.07 (95% CI: 1.00-1.14, p-value = 0.06)-i.e., no beneficial effect for copper was observed per 1 SD increase in exposure. Similarly minimal evidence was obtained for the hospitalization and critical illness outcomes with OR from 0.98 (95% CI: 0.87-1.09, p-value = 0.66) for vitamin K1 to 1.07 (95% CI: 0.88-1.29, p-value = 0.49) for copper, and from 0.93 (95% CI: 0.72-1.19, p-value = 0.55) for vitamin K1 to 1.21 (95% CI: 0.79-1.86, p-value = 0.39) for zinc, respectively. Conclusions: This study does not provide evidence that supplementation with zinc, selenium, copper or vitamin K1 can prevent SARS-CoV-2 infection, critical illness or hospitalization for COVID-19.

Essential metals, vitamins and antioxidant enzyme activities in COVID-19 patients and their potential associations with the disease severity.

The role of micronutrient deficiency in the pathogenesis of COVID-19 has been reviewed in the literature; however, the data are limited and conflicting. This study investigated the association between the status of essential metals, vitamins, and antioxidant enzyme activities in COVID-19 patients and disease severity. We recruited 155 patients, who were grouped into four classes based on the Adults guideline for the Management of Coronavirus Disease 2019 at King Faisal Specialist & Research Centre (KFSH&RC): asymptomatic (N = 16), mild (N = 49), moderate (N = 68), and severe (N = 22). We measured serum levels of copper (Cu), zinc (Zn), selenium (Se), vitamin D3, vitamin A, vitamin E, total antioxidant capacity, and superoxide dismutase (SOD). Among the patients, 30%, 25%, 37%, and 68% were deficient in Se (< 70.08 µg/L), Zn (< 0.693 µg/mL), vitamin A (< 0.343 µg/mL), and vitamin D3 (< 20.05 µg/L), respectively, and SOD activity was low. Among the patients, 28% had elevated Cu levels (> 1.401 µg/mL, KFSH&RC upper reference limit). Multiple regression analysis revealed an 18% decrease in Se levels in patients with severe symptoms, which increased to 30% after adjusting the model for inflammatory markers. Regardless of inflammation, Se was independently associated with COVID-19 severity. In contrast, a 50% increase in Cu levels was associated with disease severity only after adjusting for C-reactive protein, reflecting its possible inflammatory and pro-oxidant role in COVID-19 pathogenesis. We noted an imbalance in the ratio between Cu and Zn, with ~ 83% of patients having a Cu/Zn ratio > 1, which is an indicator of inflammation. Cu-to-Zn ratio increased to 45% in patients with mild symptoms and 34%-36% in patients with moderate symptoms compared to asymptomatic patients. These relationships were only obtained when one of the laboratory parameters (lymphocyte or monocyte) or inflammatory markers (neutrophil-to-lymphocyte ratio) was included in the regression model. These findings suggest that Cu/Zn might further exacerbate inflammation in COVID-19 patients and might be synergistically associated with disease severity. A 23% decrease in vitamin A was seen in patients with severe symptoms, which disappeared after adjusting for inflammatory markers. This finding may highlight the potential role of inflammation in mediating the relationship between COVID-19 severity and vitamin A levels. Despite our patients' low status of Zn, vitamin D3, and antioxidant enzyme (SOD), there is no evidence of their role in COVID-19 progression. Our findings reinforce that deficiency or excess of certain micronutrients plays a role in the pathogenesis of COVID-19. More studies are required to support our results.

Serum selenium concentrations and risk of all-cause and heart disease mortality among individuals with type 2 diabetes.

BACKGROUND: The impact of selenium status on the long-term health of people with type 2 diabetes (T2D) remains unclear. OBJECTIVES: To prospectively examine the association of serum selenium concentrations with all-cause and heart disease mortality among individuals with T2D. METHODS: This analysis included 3199 adults with T2D from the third NHANES (NHANES III) and NHANES (2003-2004, 2011-2014). Mortality from heart disease and all causes was linked to National Death Index mortality data. Cox proportional hazard models were used to estimate HRs and 95% CIs. RESULTS: The median (IQR) concentration of serum selenium was 127.0 (115.0, 139.1) µg/L. During an average 12.6-y follow-up, 1693 deaths were documented, including 425 heart disease deaths. Compared with participants in the lowest quartile of selenium, the multivariate-adjusted HRs (95% CIs) for participants in the highest quartile were 0.69 (0.54, 0.89) for all-cause mortality (P-trend = 0.002) and 0.66 (0.45, 0.99) for heart disease mortality (P-trend = 0.03). In addition, a linear dose-response relation between serum selenium (range: 89-182 µg/L) and mortality was observed. For per-unit increment in natural log-transformed serum selenium, there was a 64% lower risk of all-cause mortality and a 66% lower risk of heart disease mortality (both P < 0.05). Similar results were observed when stratifying by age, sex, race, smoking status, BMI, physical activity, diabetes duration, and HbA1c concentrations. CONCLUSIONS: Our study suggested that higher selenium concentration was associated with lower all-cause and heart disease mortality among individuals with T2D. More studies are needed to confirm these findings.

Plasma selenium and the risk of first stroke in adults with hypertension: a secondary analysis of the China Stroke Primary Prevention Trial.

BACKGROUND: Previous studies have indicated that selenium (Se) may play an important role in cardio-cerebrovascular disease. However, the relation between circulating selenium and risk of first stroke remains inconclusive. OBJECTIVES: We conducted a secondary analysis of the China Stroke Primary Prevention Trial (CSPPT), using a nested case-control design, and aimed to investigate the correlation between Se concentration and first stroke risk in adults with hypertension and examine the potential effect modifiers. METHODS: In the CSPPT, a total of 20,702 adults with hypertension were randomly assigned to a double-blind daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. A total of 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site were included in this study. RESULTS: During a median follow-up duration of 4.5 y (IQR: 4.2-4.6 y), there was a significant inverse association between plasma Se and the risk of first stroke (per SD increment; adjusted OR: 0.81; 95% CI: 0.68, 0.96) and ischemic stroke (per SD increment; adjusted OR: 0.76; 95% CI: 0.62, 0.93). Furthermore, a stronger inverse association between plasma Se and first stroke was observed in participants with higher folate concentrations at baseline [≥7.7 ng/mL (median), adjusted OR: 0.67; 95% CI: 0.54, 0.85, compared with <7.7 ng/mL, adjusted OR: 0.98; 95% CI: 0.80, 1.21; P-interaction = 0.008] and those with higher time-averaged systolic blood pressure (SBP) over the treatment period (≥140 mm Hg, adjusted OR: 0.71; 95% CI: 0.58, 0.86, compared with <140 mm Hg, adjusted OR: 0.96; 95% CI: 0.77, 1.20; P-interaction = 0.023). CONCLUSIONS: There was a significant inverse association between plasma Se and risk of first stroke in Chinese adults with hypertension, especially among those with higher baseline folate concentrations and those with higher time-averaged SBP over the treatment period. This trial was registered at clinicaltrials.gov as NCT00794885.

Selenium and cancer risk: Wide-angled Mendelian randomization analysis.

Evidence on the association between selenium and cancer risk is inconclusive. We conducted a Mendelian randomization study to examine the associations of selenium levels with 22 site-specific cancers and any cancer. Single nucleotide polymorphisms (SNPs) strongly associated with toenail and blood (TAB) and blood selenium levels in mild linkage disequilibrium (r2 < .3) were used as instrumental variables. Genetic associations of selenium-associated SNPs with cancer were obtained from the UK Biobank including a total of 59 647 cancer cases and 307 914 controls. Associations with P < .1 in UK Biobank were tested for replication in the FinnGen consortium comprising more than 180 000 individuals. The inverse-variance weighted method accounting for linkage disequilibrium was used to estimate the associations. Genetically predicted TAB selenium levels were not associated with the risk of the 22 site-specific cancers or any cancer (all 22 site-specific cancers). Similarly, we observed no strong association for genetically predicted blood selenium levels. However, genetically predicted blood selenium levels showed suggestive associations with risk of kidney cancer (odds ratio [OR] per one-unit increase in log-transformed levels: 0.83; 95% confidence interval [CI]: 0.67-1.03) and multiple myeloma (OR: 1.40; 95% CI: 1.02-1.93). The same direction of association for kidney cancer but not for multiple myeloma was observed in FinnGen. In the metaanalysis of UK Biobank and FinnGen, the OR of kidney cancer was 0.83 (95% CI: 0.69-1.00). Our study suggests that high selenium status may not prevent cancer development. The associations for kidney cancer and multiple myeloma need to be verified in well-powered studies.

Prenatal metal mixture concentrations and reward motivation in children.

Reward motivation is a complex umbrella term encompassing the cognitions, emotions, and behaviors involved in the activation, execution, and persistence of goal-directed behavior. Altered reward motivation in children is characteristic of many neurodevelopmental and psychiatric disorders. Previously difficult to operationalize, the Progressive Ratio (PR) task has been widely used to assess reward motivation in animal and human studies, including children. Because the neural circuitry supporting reward motivation starts developing during pregnancy, and is sensitive to disruption by environmental toxicants, including metals, the goal of this study was to examine the association between prenatal concentrations of a mixture of neurotoxic metals and reward motivation in children. We measured reward motivation by administering a PR test to 373 children ages 6-8 years enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) Study in Mexico City. Children were asked to press a response lever for a token reward; one press on the response lever was required to earn the first token and each subsequent token required an additional 10 lever presses. Maternal blood concentrations of lead, manganese, zinc, arsenic, cadmium, and selenium were measured using inductively-coupled plasma mass spectrometry during the 2nd and 3rd trimesters of pregnancy. We performed generalized Weighted Quantile Sum (gWQS) regression analyses to examine associations between the prenatal metal mixture and reward motivation; adjusting for child sex, birthweight and age; and maternal IQ, education, and socioeconomic status. The prenatal metal mixture was significantly associated with higher motivation as indicated by more lever presses (ß = 0.02, p < 0.001) and a shorter time between receiving the reinforcer and the first press (ß = 0.23, p = 0.01), and between subsequent presses (ß = 0.07, p = 0.005). Contributions of different metals to this association differed by trimester and child sex. These findings suggest that children with increased exposure to metal during the 2nd and 3rd trimesters of gestation demonstrate increased reward motivation, which may reflect a tendency to perseverate or hypersensitivity to positive reinforcement.

Natural Autoimmunity to Selenoprotein P Impairs Selenium Transport in Hashimoto's Thyroiditis.

The essential trace element selenium (Se) is needed for the biosynthesis of selenocysteine-containing selenoproteins, including the secreted enzyme glutathione peroxidase 3 (GPX3) and the Se-transporter selenoprotein P (SELENOP). Both are found in blood and thyroid colloid, where they serve protective functions. Serum SELENOP derives mainly from hepatocytes, whereas the kidney contributes most serum GPX3. Studies using transgenic mice indicated that renal GPX3 biosynthesis depends on Se supply by hepatic SELENOP, which is produced in protein variants with varying Se contents. Low Se status is an established risk factor for autoimmune thyroid disease, and thyroid autoimmunity generates novel autoantigens. We hypothesized that natural autoantibodies to SELENOP are prevalent in thyroid patients, impair Se transport, and negatively affect GPX3 biosynthesis. Using a newly established quantitative immunoassay, SELENOP autoantibodies were particularly prevalent in Hashimoto's thyroiditis as compared with healthy control subjects (6.6% versus 0.3%). Serum samples rich in SELENOP autoantibodies displayed relatively high total Se and SELENOP concentrations in comparison with autoantibody-negative samples ([Se]; 85.3 vs. 77.1 µg/L, p = 0.0178, and [SELENOP]; 5.1 vs. 3.5 mg/L, p = 0.001), while GPX3 activity was low and correlated inversely to SELENOP autoantibody concentrations. In renal cells in culture, antibodies to SELENOP inhibited Se uptake. Our results indicate an impairment of SELENOP-dependent Se transport by natural SELENOP autoantibodies, suggesting that the characterization of health risk from Se deficiency may need to include autoimmunity to SELENOP as additional biomarker of Se status.

Alcohol Consumption Moderated the Association Between Levels of High Blood Lead or Total Urinary Arsenic and Bone Loss.

Metal exposure and lifestyle are important risk factors for osteoporosis. Our study aimed to investigate the association between red blood cell lead and cadmium, total urinary arsenic, and plasma selenium levels and bone mineral density (BMD). In addition, we explored whether alcohol and coffee consumption modified the association between BMD and metals and metalloids. In total, 437 participants who underwent adult or senile physical examinations were recruited. Bone loss was defined as a calcaneus BMD T-score of <-1. Blood cadmium and lead and plasma selenium levels were measured using inductively coupled plasma mass spectrometry. Levels of urinary arsenic species were determined using high-performance liquid chromatography-hydride generator-atomic absorption spectrometry. The total urinary arsenic level was defined as the sum of the levels of urinary arsenic species. The BMD T-scores decreased significantly with increasing blood lead levels. The BMD T-scores also showed a downward trend with increasing total urinary arsenic levels. The odds ratio (OR) and 95% confidence interval (CI) for bone loss in patients with blood lead levels >57.58 versus 35.74 µg/dL were 1.98 and 1.17-3.34. In addition, the greater the lead or arsenic exposure and alcohol intake was the higher the OR for bone loss with multivariate ORs of 2.57 (95% CI 1.45-4.56) and 2.96 (95% CI 1.67-5.22), respectively. To the best of our knowledge, this study is the first to demonstrate that high total urinary arsenic or blood lead levels and frequent or occasional alcohol consumption had a significant multiplicative interaction for increasing the OR for bone loss.

Daily Intake and Serum Levels of Copper, Selenium and Zinc According to Glucose Metabolism: Cross-Sectional and Comparative Study.

Trace elements play an important role in metabolism. We compared the daily intake and serum concentrations of copper (Cu), selenium (Se), and zinc (Zn) across a spectrum of glucose tolerance status in a representative U.S. population. Daily intake and serum concentrations of Cu, Zn and Se in 5087 adults from the 2011-2016 National Health and Nutrition Examination Survey (NHANES) were examined and compared to normal (NGT) and abnormal (AGT) glucose tolerance and the presence of diabetes mellitus (DM). Other than Zn deficiency (21.15%), the prevalence of Zn, Se, and Cu excess and Se and Cu deficiency were low (<4.00%). As compared to the NGT group, Cu and Se supplementation was higher in the AGT and DM groups (p < 0.0001 for all). Serum Se and Zn, but not Cu, concentrations were highly correlated with daily intake (p < 0.0001 for both). As compared to the NGT group, serum Cu concentration was highest in the AGT group (p = 0.03), serum Se concentration was highest in the DM group (p < 0.0001), and serum Zn concentration was highest in the AGT group (p < 0.0001). Serum Se and Zn concentration was correlated with daily Se and Zn intake. Even within the reference range for serum Cu, Se, and Zn concentrations, a higher serum concentration of Cu, Se, and Zn was associated with abnormal glucose metabolism. Although the casual relationship remains to be elucidated, these data suggest caution in Cu, Se and Zn supplementation in non-deficient individuals.

Course and Survival of COVID-19 Patients with Comorbidities in Relation to the Trace Element Status at Hospital Admission.

Selenium (Se) and zinc (Zn) are essential trace elements needed for appropriate immune system responses, cell signalling and anti-viral defence. A cross-sectional observational study was conducted at two hospitals in Ghent, Belgium, to investigate whether Se and/or Zn deficiency upon hospital admission correlates to disease severity and mortality risk in COVID-19 patients with or without co-morbidities. Trace element concentrations along with additional biomarkers were determined in serum or plasma and associated to disease severity and outcome. An insufficient Se and/or Zn status upon hospital admission was associated with a higher mortality rate and a more severe disease course in the entire study group, especially in the senior population. In comparison to healthy European adults, the patients displayed strongly depressed total Se (mean ± SD: 59.2 ± 20.6 vs. 84.4 ± 23.4 µg L-1) and SELENOP (mean ± SD: 2.2 ± 1.9 vs. 4.3 ± 1.0 mg L-1) concentrations at hospital admission. Particularly strong associations were observed for death risk of cancer, diabetes and chronic cardiac disease patients with low Se status, and of diabetes and obese patients with Zn deficiency. A composite biomarker based on serum or plasma Se, SELENOP and Zn at hospital admission proved to be a reliable tool to predict severe COVID-19 course and death, or mild disease course. We conclude that trace element assessment at hospital admission may contribute to a better stratification of patients with COVID-19 and other similar infectious diseases, support clinical care, therapeutic interventions and adjuvant supplementation needs, and may prove of particular relevance for patients with relevant comorbidities.