Blood Metal Research Articles

Use of biomarkers of metals to improve prediction performance of cardiovascular disease mortality

BackgroundWhether including additional environmental risk factors improves cardiovascular disease (CVD) prediction is unclear. We attempted to improve CVD mortality prediction performance beyond traditional CVD risk factors by additionally using metals measured in the urine and blood and with statistical machine learning methods.MethodsOur sample included 7,085 U.S. adults aged 40 years or older from the National Health and Nutrition Examination Survey 2003–2004 through 2015–2016, linked with the National Death Index through December 31, 2019. Data were randomly split into a 50/50 training dataset used to construct CVD mortality prediction models (n = 3542) and testing dataset used as validation to assess prediction performance (n = 3543). Relative to the traditional risk factors (age, sex, race/ethnicity, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol, hypertension, and diabetes), we compared models with an additional 17 blood and urinary metal concentrations. To build the prediction models, we used Cox proportional hazards, elastic-net (ENET) penalized Cox, and random survival forest methods.Results420 participants died from CVD with 8.8 mean years of follow-up. Blood lead, cadmium, and mercury were associated (p < 0.005) with CVD mortality. Including these blood metals in a Cox model, initially containing only traditional risk factors, raised the C-index from 0.845 to 0.847. Additionally, the Net Reclassification Index showed that 23% of participants received a more accurate risk prediction. Further inclusion of urinary metals improved risk reclassification but not risk discrimination.ConclusionsIncorporating blood metals slightly improved CVD mortality risk discrimination, while blood and urinary metals enhanced risk reclassification, highlighting their potential utility in improving cardiovascular risk assessments.

Maternal and Cord Blood Levels of Metals and Fetal Liver Function

Exposure to metals during pregnancy has been associated with adverse birth outcomes, but its impact on fetal liver function remains poorly understood. This study for the first time aimed to investigate the association between maternal and umbilical cord blood Metals levels and umbilical liver enzymes. A comprehensive analysis was conducted on 450 mother-newborn pairs in 2022, measuring 13 Metals in serum samples from pregnant women during the third trimester and umbilical cord blood samples. Regression analyses were utilized to examine the relationship between levels of maternal and umbilical cord blood Metals and the levels of gamma-glutamyl transferase (GGT), umbilical alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). G-comp analyses evaluated the combined effect of metals exposure on umbilical liver enzymes. Elevated levels of certain Metals in cord blood and maternal samples were positively linked with increased umbilical GGT, ALP, ALT, and AST levels. Notably, zinc (Zn) levels in cord blood exhibited an inverse correlation with umbilical liver enzyme levels. Furthermore, g-comp analyses revealed significant positive associations between exposure to metals mixtures and umbilical liver enzyme levels. An increase of one quartile in the mixture of maternal and umbilical Metals was linked with 99.45 U/L (95% CI:37.72, 161.19, p < 0.01), 2.79 (95% CI: 0.92, 4.65, p < 0.01), and 87.17 (95% CI: 53.96, 120.38, p < 0.01) increase in ALP, ALT and GGT levels. Further examination of the weight of Metals revealed As, Cd, Ni, Pb, Hg and Cr with the highest positive effects and Zn with the highest negative effect in the mixture effect on the umbilical liver enzyme. In summary, our results underscore the potential influence of prenatal heavy metal exposure on fetal liver function.

Associations of mixed metals exposure with cognitive impairment risk: a cross-sectional study in Chinese adults.

Associations between exposure to single metals and cognitive impairment or related outcomes have been reported in many previous studies. However, co-exposure to more than one metal is common situation. In recent years, studies on the effects of exposure to multiple metals on cognitive impairment or related outcomes have increased, but remain very limited, with a focus on populations with occupational exposure to metals, children, and adolescents. The potential relationships between exposure to metal mixtures and risk of cognitive impairment in adults remain to be clarified. To determine the associations between blood metal mixtures and cognitive impairment risk. Inductively coupled plasma mass spectrometry (ICP-MS) was utilized to detect the blood levels of lead (Pb), iron (Fe), copper (Cu), calcium (Ca), magnesium (Mg), and zinc (Zn). Multivariable logistic regression and Bayesian kernel machine regression (BKMR) models were employed to assess the relationships of exposure to these blood metal mixtures with the risk of cognitive impairment. It was found that four metals (Pb, Fe, Cu, and Mg) were positively correlated with cognitive impairment in each single metal model. The association of Pb and Cu remained significant after adjusting for these six metals, with the odds ratios (95% confidence intervals) in the highest quartiles of 9.51 (4.41-20.54, p-trend <0.01) and 4.87 (2.17-10.95, p-trend <0.01), respectively. The BKMR models indicated that co-exposure levels of Ca, Cu, Fe, Mg, Pb, and Zn were related to increased risk of cognitive impairment at ≥25th percentile compared with median, and Pb and Cu mainly contributed to the joint effect. In addition, the interaction effects of Mg and Pb/Pb and Cu on the risk of cognitive impairment were observed. Co-exposure of six metals (Pb, Fe, Cu, Ca, Mg, and Zn) increased the risk of cognitive impairment in Chinese adults, with Pb and Cu likely to have greater impact. Potential interaction effects of Mg and Pb, Pb and Cu on the risk of cognitive impairment may exist.

A cross-sectional study of the association between blood metal mixtures exposure and hyperuricemia.

To determine the association between blood metal mixture and HUA risk. A cross-sectional study was performed based on the populations from Kailuan cohort trial in China. Inductively coupled plasma mass spectrometry was utilized to detect the blood concentrations of iron (Fe), lead (Pb), calcium (Ca), copper (Cu), magnesium (Mg), zinc (Zn), selenium (Se), and manganese (Mn). Multivariate logistic regression (MLR) models and weighted quantile sum (WQS) regression models were employed to assess the relationships. There were 3706 participants included in this study, and 464 (12.52%) were with HUA. The mean level of uric acid was 485.60μmol/L in the subjects with HUA, which was remarkably increased compared to those without HUA (293.10μmol/L). The multivariate-adjusted odds ratios (95% confidence intervals) of HUA were 2.15 (1.40, 3.29) for Pb, 3.42 (2.24, 5.23) for Fe, 1.61 (1.15, 2.25) for Ca, 3.06 (2.04, 4.59) for Mg, and 1.69 (1.26, 2.28) for Zn by comparing the highest and lowest metal quartiles using the single-metal logistic regression model. Meanwhile, the WQS regression models demonstrated a positive association between metal mixtures and HUA risk, to which, Fe, Mg, Pb, and Zn were the major contributors. Pb, Fe, and Zn were still robust in multiple-metal models. Age, gender, weight, smoking, and drinking status could modify these relationships with significant interactions. Co-exposure to Fe, Pb, Ca, Cu, Zn, Mg, Se, and Mn were related to increased HUA risk in Chinese adults, of with, Pb, Fe, and Zn appeared to have greater impacts. These relationships were more obvious in adults aged < 60years, or women, or overweight, or non-smoking, or drinking with significant interactions. Key Points • Increased Fe, Pb, Mg, Ca, and Zn were related to increased HUA risk in dose-response fashion among Chinese adults. • The metal mixture dominated by Fe, Mg, Pb, and Zn was positively associated with HUA risk. Fe, Pb, and Zn were still robust in MM model. • Such association was stronger showed in adults aged < 60years, or women, or overweight, or non-smoking, or drinking with significant interactions.

Heavy Metals in Umbilical Cord Blood: Effects on Epigenetics and Child Development.

Heavy metals like arsenic, mercury, cadmium, and lead are harmful pollutants that can change how our genes are regulated without altering the DNA sequence, specifically through a process called DNA methylation (DNAm) at 5-methylcytosine, an epigenetic mark that we will focus on in this review. These changes in DNAm are most sensitive during pregnancy, a critical time for development when these modifications can affect how traits are expressed. Historically, most research on these environmental effects has focused on adults, but now there is more emphasis on studying the impacts during early development and childhood. The placenta acts as a protective barrier between the mother and the baby, and by examining it, scientists can identify changes in key genes that might affect long-term health. This review looks at how exposure to heavy metals during pregnancy can cause changes in the gene regulation by DNAm in newborns, as seen in their umbilical cord blood. These changes reflect the baby's genetic state during pregnancy and can be influenced by the mother's environment and genetics, as well as the baby's own genetics.

B-158 Association between multiple heavy metals exposure and blood lipid levels: evidence from a cross-sectional study of Korean adults

Abstract Background Metals are ubiquitous in our environment and enter human body via various pathways, such as air, soil, food, water, etc. Increasing studies have found that metals are important risk factors in developing dyslipidemia. However, there is no consensus regarding the effects of co-exposure to multiple metals on blood lipid levels. We investigated both the joint and individual effects of this metal mixture exposure on human blood lipid levels. Methods Blood concentrations of four human toxic metals (Pb, Cs, Hg, and Cd) in 2,798 general populations from Korea were simultaneously determined as a measure of exposure. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to estimate associations of four blood metals and metals mixture with lipid profiles, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Results The mean age of the overall study population was 41.2 ± 9.85 years, and 66.9% were men. The prevalence of overweight or obesity, diabetes, and hypertension in the population was 62.5, 6.8, and 13.9%, respectively. In the multivariable linear regression model, the blood Cs was positively associated with TC and LDL-C(p &amp;lt; 0.05, all), and the blood Pb was positively associated with serum TG (p &amp;lt; 0.05, all). Also, the blood Cd was positively associated with serum HDL-C (p &amp;lt; 0.05, all). We did not identify any other obvious interaction between metals on the lipid profiles using a bivariate exposure-response function in BKMR. Conclusions Our finding suggests that combined exposure to this metal mixture may affect human blood lipid levels. Therefore, reducing exposure to heavy metals, such as Cs and Pb, should be a priority for the general population. However, future studies with a larger number of heavy metals are still needed to focus on the detrimental effects of single metals on lipid profiles as well as to identify key components.

Effects of Mixed Metal Exposure on MRI Metrics in Basal Ganglia.

Welding fumes contain various metals. Past studies, however, mainly focused on Manganese (Mn)-related neurotoxicity. This study investigated welding-related mixed metal exposure effects on MRI metrics in the basal ganglia (BG) and their dose-response relationship. Subjects with (N = 23) and without (N = 24) a welding exposure history were examined. Metal exposure was estimated with exposure history questionnaire and whole blood metal levels. T1 (weighted-intensity and relaxation time; estimates of brain Mn accumulation), diffusion tensor imaging [Axial (AD), mean (MD), radial diffusivity (RD), and fractional anisotropy (FA); estimates of microstructural differences] metrics in BG [caudate nucleus, putamen, and globus pallidus (GP)] and voxel-based morphometry (for volume) were examined and related with metal exposure measures. Compared to controls, welders showed higher GP R1 (1/T1; p = 0.034) but no differences in blood metal and T1-weighted (T1W) values in any ROIs (p's > 0.120). They also had higher AD and MD values in the GP (p's < 0.033) but lower FA values in the putamen (p = 0.039) with no morphologic differences. In welders, higher blood Mn and Vanadium (V) levels predicted higher BG R1 and T1W values (p's < 0.015). There also were significant overall metal mixture effects on GP T1W and R1 values. Moreover, GP AD and MD values showed non-linear associations with BG T1W values: They increased with increasing T1W values only above certain threshold of T1 values. The current findings suggest that Mn and V individually but also metal mixtures jointly predict GP T1 signals that may in turn contribute to altered DTI metrics in the BG after certain exposure threshold levels.

Exposure to Multiple Metal(loid)s and Hypertension in Chinese Older Adults.

Evidence about effects of metal(loid)s on hypertension among adults is insufficient. The aim of our study was to evaluate the individual and joint associations between seven selected metal(loid)s and hypertension, including lead (Pb), manganese (Mn), nickel (Ni), arsenic (As), cadmium (Cd), chromium (Cr), and vanadium (V)) in Chinese older adults. This study included 1009 older adults, and the blood concentrations of seven metal(loid)s were evaluated by inductively coupled plasma mass spectrometry (ICP-MS). The following conditions were considered as hypertension: (1) either systolic blood pressure ≥ 140mm Hg or diastolic blood pressure ≥ 90mm Hg, (2) a self-reported history of hypertension, or (3) currently taking antihypertensive medications. Logistic regression was utilized to investigate the association between individual metal(loid) and hypertension, while Bayesian kernel machine regression (BKMR) was employed to investigate the association of the metal(loid) mixture with hypertension. Adjusted single-metal(loid) model showed a significant positive association between Pb and hypertension (OR = 1.24, 95%CI = 1.03-1.50). This significant association still existed in multi-metal(loid) model (OR = 1.22, 95%CI = 1.01-1.47). BKMR further indicated a positive linear association of Pb with hypertension. The metal(loid) mixture was positively associated with hypertension in older adults, although not significant. Within the mixture, Pb had the highest posterior inclusion probabilities value (PIP = 0.9192). There were multiplicative interactions of Pb and Mn on hypertension. In addition, Pb and Mn had additive effects on the association of other blood metal(loid)s with hypertension. The associations of multiple metal(loid)s with hypertension are dependent on diabetes, areas, age, and BMI. The metal(loid) mixture exposure may contribute to hypertension in Chinese older adults, mainly driven by Pb and interactions of Pb and Mn. Reducing exposure to these metal(loid)s may prevent hypertension among older adults, which is especially true for those living with diabetes.

Investigating the relationship of co-exposure to multiple metals with chronic kidney disease: An integrated perspective from epidemiology and adverse outcome pathways

Systematic studies on the associations between co-exposure to multiple metals and chronic kidney disease (CKD), as well as the underlying mechanisms, remain insufficient. This study aimed to provide a comprehensive perspective on the risk of CKD induced by multiple metal co-exposures through the integration of occupational epidemiology and adverse outcome pathway (AOP). The study participants included 401 male mine workers whose blood metal, β2-microglobulin (β2-MG), and cystatin C (Cys-C) levels were measured. Generalized linear models (GLMs), quantile g-computation models (qgcomp), least absolute shrinkage and selection operator (LASSO), and bayesian kernel machine regression (BKMR) were utilized to identify critical nephrotoxic metals. The mean concentrations of lead, cadmium, mercury, arsenic, and manganese were 191.93, 3.92, 4.66, 3.11, 11.35, and 16.33 µg/L, respectively. GLM, LASSO, qgcomp, and BKMR models consistently identified lead, cadmium, mercury, and arsenic as the primary contributors to kidney toxicity. Based on our epidemiological analysis, we used a computational toxicology method to construct a chemical-genetic-phenotype-disease network (CGPDN) from the Comparative Toxicogenomics Database (CTD), DisGeNET, and GeneCard databases, and further linked key events (KEs) related to kidney toxicity from the AOP-Wiki and PubMed databases. Finally, an AOP framework of multiple metals was constructed by integrating the common molecular initiating events (reactive oxygen species) and KEs (MAPK signaling pathway, oxidative stress, mitochondrial dysfunction, DNA damage, inflammation, hypertension, cell death, and kidney toxicity). This is the first AOP network to elucidate the internal association between multiple metal co-exposures and CKD, providing a crucial basis for the risk assessment of multiple metal co-exposures.

Association between blood heavy metal element and all-cause mortality in asthmatic adults: a cohort study

Asthma start, development, and exacerbation have all been linked in numerous studies to exposure to a variety of metal elements. However, there is still a dearth of epidemiological data linking heavy metal exposure to death in asthmatics. The investigation included 2432 eligible adults with asthma. The study examined the possible correlation between blood heavy metal levels and all-cause mortality. This was done by utilizing Cox proportional hazards models, restricted cubic spline (RCS), threshold effect models, and CoxBoost models. Subgroup analyses were conducted to investigate the associations between blood metal levels and all-cause mortality among distinct asthmatic populations. An inverse association was found between blood selenium and all-cause mortality in asthmatics, while blood manganese showed a positive association with all-cause mortality. However, there were no significant connections found between blood lead, cadmium, mercury, and all-cause mortality via multivariate Cox proportional hazard models. In model 3, after accounting for all factors, all-cause mortality dropped by 10% for every additional 10 units of blood selenium (μg/L) and increased by 6% for every additional unit of blood manganese (μg/L). The RCS and threshold effect model found a U-shaped correlation between blood selenium, blood manganese, and all-cause mortality. The lowest all-cause mortality among asthmatics was observed when blood selenium and manganese were 188.66 μg/L and 8.47 μg/L, respectively. Our investigation found a U-shaped correlation between blood selenium levels, blood manganese levels, and all-cause mortality in asthmatic populations. Optimizing dietary selenium intake and effectively managing manganese exposure could potentially improve the prognosis of asthma.

The association of mixed multi-metal exposure with sleep duration and self-reported sleep disorder: A subgroup analysis from the National Health and Nutrition Examination Survey (NHANES)

Sleep disorders significantly affect sleep duration and constitute a major public health issue. However, the relationship between metal exposure and sleep is not fully elucidated. This study utilized publicly available data from the National Health and Nutrition Examination Survey (NHANES) to measure blood concentrations of seven metals—copper (Cu), zinc (Zn), selenium (Se), manganese (Mn), mercury (Hg), cadmium (Cd), and lead (Pb)—in a cohort of 4263 American adults. The relationship between metal exposure and self-reported sleep duration and sleep disorder risk was analyzed using single exposure models like logistic and linear regression and mixedexposure models such as weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR). The results indicated an absence of statistically significant findings in the single exposure model. In contrast, the mixed exposure model revealed a positive correlation between selenium levels and the risk of sleep disorders across the entire population. A “U-shaped” association was identified between copper levels and the risk of sleep disorders in males, females, and individuals aged 60 and above. Moreover, a positive trend was observed between manganese levels and the risk of sleep disorders in individuals aged 60 and above. Additionally, elevated concentrations of metal mixtures were significantly associated with reduced sleep duration among females. Sensitivity analyses corroborated these findings. In conclusion, within the context of metal mixtures, selenium may be a risk factor for sleep disorders in the general population. Manganese may be a unique risk factor in older adults. Copper levels have a “U" shaped link to sleep disorder risk in specific population subgroups. Finally, the accumulation of blood metal mixtures in females, mainly due to lead and mercury, may reduce sleep duration. Further research is necessary to validate these findings.

Blood metal concentrations and cardiac structure and function in total joint arthroplasty patients.

There is concern regarding potential long-term cardiotoxicity with systemic distribution of metals in total joint arthroplasty (TJA) patients. To determine the association of commonly used implant metals with echocardiographic measures in TJA patients. The study comprised 110 TJA patients who had a recent history of high chromium, cobalt or titanium concentrations. Patients underwent two-dimensional, three-dimensional, Doppler and speckle-strain transthoracic echocardiography and a blood draw to measure metal concentrations. Age and sex-adjusted linear and logistic regression models were used to examine the association of metal concentrations (exposure) with echocardiographic measures (outcome). Higher cobalt concentrations were associated with increased left ventricular end-diastolic volume (estimate 5.09; 95%CI: 0.02-10.17) as well as left atrial and right ventricular dilation, particularly in men but no changes in cardiac function. Higher titanium concentrations were associated with a reduction in left ventricle global longitudinal strain (estimate 0.38; 95%CI: 0.70 to 0.06) and cardiac index (estimate 0.08; 95%CI, -0.15 to -0.01). Elevated cobalt and titanium concentrations may be associated with structural and functional cardiac changes in some patients. Longitudinal studies are warranted to better understand the systemic effects of metals in TJA patients.

Associations of multiple blood metals with cardiac structure and function: A cross-sectional study in a CAD population

Coronary artery disease (CAD) is often accompanied by abnormal cardiac structure and function, leading to an increased prognostic risk. However, less is known about the associations of mixed metals with abnormal cardiac structure and function in CAD patients. Here, we aimed to investigate the associations of exposure to metal mixtures with cardiac structure and function and potential interactions in a CAD population. We conducted a cross-sectional study from Southwest China that included 1555 CAD patients. The blood concentrations of 14 metals were measured via inductively coupled plasma spectrometry. CAD was defined as at least one vessel having stenosis ≥50% the vessel diameter. Echocardiography was used for cardiac structural and functional measurements. Bayesian kernel machine regression was applied to explore the overall effect, metal weight, and dose effect. Linear regression analysis was used to analyze the effects of single metals, metal‒metal interactions and metal‒traditional interactions. Finally, we found that the negative associations of mixed metals with cardiac structure was significant when the levels of all metals were below the 60th percentile. For cardiac function, changes in metals from 50th to 75th were associated with 0.954% and 0.683% decrease in left ventricular ejection fraction and left ventricular fractional shortening, respectively. Negative associations of copper and manganese with cardiac structure and function, whereas positive associations of titanium, selenium and molybdenum with several parameters were found. Antagonistic interactions between copper and tin and between selenium and several metals (manganese, copper and aluminum) (all Pinteraction terms < 0.05) were found. In conclusion, mixed metal exposure was negatively associated with cardiac structure and function in CAD patients. The main metals contributing to this negative associations were copper and manganese. Selenium or tin supplementation may reduce the adverse associations of copper and manganese with cardiac structure and function.

Association between blood lead, cadmium, selenium levels and hyperlipidemia: A population-based study.

There are limited epidemiological investigations of blood metal levels related to hyperlipidemia, and results indicating the association between blood lead (Pb), cadmium (Cd) and selenium (Se), and lipid biomarkers have been conflicting. We included populations for which NHANES collected complete data. Multivariate logistic regression and subgroup analyses were conducted to ascertain the relationship between blood Pb, Cd, and Se levels and hyperlipidemia. Nonlinear relationships were characterized by smoothed curve fitting and threshold effect analysis. 5429 participants in all, with a mean age of 53.70 ± 16.63 years, were included; 47.1% of the subjects were male, and 3683 (67.8%) of them had hyperlipidemia. After modifying for variables with confounders in a multivariate logistic regression model, we discovered a positive correlation between blood Pb and Se levels and hyperlipidemia (Pb: OR:2.12, 95% CI:1.56-2.88; Se: OR:1.84, 95% CI:1.38-2.45). Gender, age, smoking status, alcohol use status, hypertension, diabetes, and body mass index were not significantly linked with this positive correlation, according to subgroup analysis and interaction test (P for interaction>0.05). Positive correlations between blood Pb, Cd, and Se levels and the risk of hyperlipidemia have been found using smooth curve fitting. This study demonstrates that higher blood levels of Pb, Cd, and selenium are linked to an increased risk of hyperlipidemia.

Blood Metal Mixture Effects on All-Cause Mortality in American Indian Populations, Strong Heart Study

Blood Metal Mixture Effects on All-Cause Mortality in American Indian Populations, Strong Heart Study

Prenatal blood metals, per- and polyfluoroalkyl substances and antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion

Prenatal blood metals, per- and polyfluoroalkyl substances and antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion

Sex-specific associations of blood metal mixtures with thyroid hormone homeostasis among Chinese adults: Evidence from a national cross-sectional study

Sex-specific associations of blood metal mixtures with thyroid hormone homeostasis among Chinese adults: Evidence from a national cross-sectional study

Association of blood cadmium, lead, and mercury with anxiety: a cross-sectional study from NHANES 2007-2012.

The purpose of this paper is to explore the relationship between blood levels of cadmium, lead, and mercury and anxiety in American adults. Blood metals and self-reported anxiety days were extracted from laboratory data and questionnaire data, respectively, using NHANES data from 2007-2012. Weighted logistic regression was used to assess the relationship between cadmium, lead and mercury with anxiety. Restricted cubic spline was used to visualize the non-linear relationship between metal concentrations and anxiety. Weighted quantile sum (WQS) regression was used to investigate the effect of combined exposure to the three metals on anxiety. The prevalence of anxiety in adults was 26.0%. After adjusting for potential confounding variables, cadmium levels in the highest quartile (Q4) were associated with a higher risk of anxiety compared to the lowest quartile (Q1) (OR = 1.279, 95% CI: 1.113-1.471, p < 0.01). Restricted cubic spline analysis indicated a positive association between blood cadmium levels and anxiety. Furthermore, co-exposure to multiple heavy metals was positively associated with anxiety risk (WQS positive: OR = 1.068, 95% CI: 1.016-1.160, p < 0.05), with cadmium contributing the most to the overall mixture effect. Compared to the Light RPA, the Vigorous/Moderate RPA group had a relatively low risk of anxiety after cadmium exposure. High levels of blood cadmium are positively associated with the development of anxiety disorders, which needs to be further verified in future studies.

Mediation analysis for TNF-α as a mediator between multiple metal exposure and kidney function

The association between metal mixtures and kidney function has been reported. However, reports on the mechanism of metal toxicity were limited. Oxidative stress was reported as a possible cause. This study aimed to determine the association between of kidney function and metals, such as arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), lead (Pb), selenium (Se), and zinc (Zn), and to explore the possible mediating role of tumor necrosis factor alpha (TNF-α) between metal toxicity and kidney function. In this study, we recruited 421 adults from a health examination. The concentration of blood metals was analyzed using inductively coupled plasma mass spectrometry. We used linear regression models to assess the association between metals and TNF-α. Then, mediation analysis was applied to investigate the relationship between metal exposure, TNF-α, and kidney function. In univariate linear regression, blood As, Cd, Co, Cu, Pb, and Zn levels significantly increased TNF-α and decreased kidney function. Higher blood As and Pb levels significantly increased TNF-α in multivariable linear regressions after adjusting for covariates. We found that blood levels of As (coefficients = −0.021, p = 0.011), Pb (coefficients = −0.060, p < 0.001), and Zn (coefficients = −0.230, p < 0.001) showed a significant negative association with eGFR in the multiple-metal model. Furthermore, mediation analysis showed that TNF-α mediated 41.7 %, 38.8 %, and 20.8 % of blood Cd, As and Pb, respectively. Among the essential elements, TNF-α mediated 24.5 %, 21.5 % and 19.9 % in the effects of blood Co, Cu, and Zn on kidney function, respectively. TNF-α, acting as a mediator, accounted for 20.1 % of the contribution between the WQS score of metal mixtures and the eGFR (p < 0.001). This study suggested that TNF-α may be a persuasive pathway mediating the association between metals and kidney function. Inflammation and kidney injury could be the underlying mechanisms of metal exposure. However, there is still a need to clarify the biochemical mechanism in follow-up studies.

Metal exposure in the Greenlandic ACCEPT cohort: follow-up and comparison with other Arctic populations

ABSTRACT Humans are exposed to metals through diet and lifestyle e.g. smoking. Some metals are essential for physiologically body functions, while others are non-essential and can be toxic to humans. This study follows up on metal concentrations in the Greenlandic ACCEPT birth-cohort (mothers and fathers) and compares with other Arctic populations. The data from 2019 to 2020 include blood metal concentrations, lifestyle and food frequency questionnaires from 101 mothers and 76 fathers, 24–55 years, living in Nuuk, Sisimiut, and Ilulissat. A high percentage (25–45%) exceeded international guidance values for Hg. For the mothers, the metal concentrations changed significantly from inclusion at pregnancy to this follow-up 3–5 years after birth; some increased and others decreased. Most metals differed significantly between mothers and fathers, while few also differed between residential towns. Several metals correlated significantly with marine food intake and socio-economic factors, but the direction of the correlations varied. Traditional marine food intake was associated positively with Se, As and Hg. To the best of our knowledge, this study provides the most recent data on metal exposure of both men and women in Greenland, elucidating metal exposure sources among Arctic populations, and documents the need for continuing biomonitoring to follow the exceeding of guidance values for Hg.