Urinary Metals Research Articles

Urinary metal mixtures and their association with renal function: A cross-sectional study in Mexico

Urinary metal mixtures and their association with renal function: A cross-sectional study in Mexico

Study on the correlation and interaction between metals and dyslipidemia: a case-control study in Chinese community-dwelling elderly.

Previous studies on the association between metals and dyslipidemia are not completely consistent. There are few studies investigating the relationship between mixed metal exposure and dyslipidemia as well as the effects of metals on dyslipidemia in community-dwelling elderly. To evaluate the correlations and interaction effect between the urinary concentrations of metals and the risk of dyslipidemia in community-dwelling elderly. We designed a case-control study to assess the correlation between urine metals and dyslipidemia in elderly people in the Yinchuan. The urinary levels of 13 metals, including calcium, vanadium, iron, cobalt, zinc, copper, arsenic, selenium, molybdenum, cadmium, tellurium, and thallium, were measured by inductively coupled plasma-mass spectrometry (ICP-MS), and the blood biochemical analyzer was used to measure the blood lipid levels of 3384 senior individuals from four different areas of Yinchuan city. Logistic regression and restricted cubic splines (RCS) were used to explore the correlation and dose-response relationship between urinary metals and the risk of dyslipidemia. Least absolute shrinkage and selection operator (LASSO) regression was used to select metals, and then weighted quantile sum (WQS) regression was used to explore the weight of each metal in mixed metals. Bayesian kernel machine regression (BKMR) was used to explore the interactions between metals on dyslipidemia risk. (1) After selection by LASSO regression, in the multi-metal model, compared with the lowest quartile, the adjusted ORs (95%CI) of the highest quartiles were 0.47 (0.37-0.60) for Fe, 1.43 (1.13-1.83) for Zn, 1.46 (1.11-1.92) for As, 0.59 (0.44-0.80) for Se, 1.53 (1.18-2.00) for Mo, and 1.36 (1.07-1.73) for Te. (2) In the WQS regression model, Fe and Mo accounted for the largest weight in the negative and positive effects of dyslipidemia, respectively. (3) In the BKMR model, there may be a positive interaction between Te and Se on dyslipidemia. Among the mixed metals, Fe, As, Se, Mo, and Te were associated with the prevalence of dyslipidemia, with Fe and Mo contributing the most. There may be certain interactions between Te and Se.

Association of co-exposure to metal(loid)s during pregnancy with birth outcomes in the Tibetan plateau

Maternal metal (loid)s exposure has been related to birth outcomes but the results are still inconclusive. Most previous studies have discussed the single metal (loid)s, neglecting the scene of co-exposure. We examined the associations of both single metal (loid)s and metal mixtures with birth outcomes in a birth cohort from the Tibetan Plateau, including body weight, body length, head circumference, small for gestational age (SGA), and Ponderal index (PI). In our analysis of 1069 women, we measured 29 metal (loid)s in urine samples in the third trimester. The associations of single metal (loid)s with categorical or continuous birth outcomes were evaluated using a generalized linear mixed-effects model or linear mixed-effects model, respectively. The least absolute shrinkage and selection operator, Bayesian kernel machine, and Quantile g-computation regression were used to explore the joint association. We also evaluated the interactive effects of ethnicity and altitude on the effect of metal (loid)s on birth outcomes. Copper (Cu) concentration in maternal urine was positively associated with SGA, birth weight, birth length, and head circumference in the single pollutant models. For instance, Cu was associated with an increased risk of SGA [OR (95% CI) = 1.56 (1.23, 1.97); P < 0.001]. We didn't find significant joint association of metal mixtures with birth outcomes except a positive association between the mixture of Cu, Magnesium (Mg), and Iron (Fe) with the risk of SGA when the exposure level was above its 80th percentile, and Cu dominated the adverse association in a non-linear manner. Living altitude modified the associations of Cu with SGA and the positive association was only found in participants living at high altitude. In conclusion, maternal urinary metal (loid)s, especially Cu, was the dominant harmful metal (loid)s when associated with SGA on the Tibetan Plateau.

Associations between urinary heavy metals and anxiety among adults in the National Health and Nutrition Examination Survey (NHANES), 2007–2012

BackgroundFew studies have investigated the associations between heavy metals and anxiety. The purpose of this study was to examine the associations between single and combined exposure to heavy metals and anxiety. MethodsThis study employed data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Anxiety was assessed by patients self-reporting the number of anxious days per month. First, we evaluated the associations between 10 heavy metals single exposure and anxiety by multivariable logistic regression. We then selected 5 heavy metals (cadmium, antimony, cobalt, tungsten, and uranium) for further analysis by elastic net regression. Subsequently, principal component analysis (PCA), weighted quantile regression (WQS), and Bayesian kernel machine regression (BKMR) were utilized to evaluate the associations between 5 heavy metals co-exposure and anxiety. ResultsThis study included 4512 participants, among whom 1206 participants were in an anxiety state. Urinary cadmium and antimony were separately related to an increased risk of anxiety (p for trend <0.01 and < 0.01, respectively). In PCA analysis, PC1 was associated with an increased risk of anxiety (p for trend <0.001). In WQS analysis, the positive WQS index was substantially linked with the risk of anxiety (OR (95%CI): 1.23 (1.04,1.39)). In BKMR analysis, the overall effects of co-exposure to heavy metals were positively connected with anxiety. ConclusionOur study identified a positive correlation between individual exposure to cadmium and antimony and the risk of anxiety. Additionally, the co-exposure to cadmium, antimony, cobalt, tungsten, and uranium was associated with an increased risk of anxiety.

Mediation analysis of urinary metals and stroke risk by inflammatory markers

BackgroundThe association between metals and stroke has been reported, but the mediating role of inflammation between metals and stroke remains unclear. MethodsWe included 9326 adults from the National Health and Nutrition Examination Survey in this study. Through least absolute selection and shrinkage operator (LASSO) regression, weighted quantile sum (WQS) regression, logistic regression, linear regression, restricted cubic spline analysis, and mediation analysis, we explored the association between metals and stroke, as well as the association between metals and inflammatory indicators, and further evaluated the mediating effect of inflammatory indicators on the association between selected metals and stroke risk. ResultsThe results of the present study suggested positive associations between mixed metals, cadmium and uranium and stroke risk. There is a positive correlation and dose‒response relationship between cadmium and C-reactive protein (CRP). Moreover, CRP mediates 10.1% of the association between cadmium and stroke. ConclusionsAt the epidemiological level, CRP mediates the association between cadmium and stroke risk, suggesting that inflammation may be a potential mechanism for metal-induced stroke.

Relationship of individual and mixed urinary metals exposure with liver function in the China National Human Biomonitoring (CNHBM) of Zhejiang Province

BackgroundHeavy metals have been reported to affect liver function. However, there is currently little and inconsistent knowledge about the effects of combined and individual urinary metals on specific parameters of liver function in the general population. Therefore, this study aimed to investigate their associations. MethodsThis study involved 807 general population from the China National Human Biomonitoring of Zhejiang Province 2017–2018. Concentrations of urinary metals, including Chromium (Cr), Cobalt (Co), Nickle (Ni), Arsenic (As), Selenium (Se), Molybdenum (Mo), Cadmium (Cd), Thallium (Tl) and Lead (Pb) were measured. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein (TP), albumin (ALB), direct bilirubin (DBIL), total bilirubin (TBIL) as liver function biomarkers. Multivariable linear regression and weighted quantile sum (WQS) regression were employed to explore the associations of urinary metals with liver function biomarkers. Subgroup analysis stratified by gender and age, excluding smokers and drinkers for sensitivity analysis. ResultsBoth statistical models indicated that urinary metals were positively associated with ALT and AST, while negatively with TP, ALB, DBIL and TBIL. In the WQS analysis, each quartile increase in the ln-transformed levels of metal mixtures was associated with 4.11 IU/L (95% CI: 1.07, 7.15) higher ALT and 3.00 IU/L (95% CI: 1.75, 4.25) higher AST, as well as, with 0.67 g/L (95% CI: 1.24, −0.11) lower TP, 0.74 g/L (95% CI: 1.09, −0.39) lower ALB, 0.38 μmol/L (95% CI: 0.67, −0.09) lower DBIL, and 1.56 μmol/L (95% CI: 2.22, −0.90) lower TBIL. The association between urinary metals and ALT was primarily driven by Cd (55.8%), Cr contributed the most to the association with AST (20.2%) and TBIL (45.2%), while the association with TP was primarily driven by Ni (38.2%), the association with ALB was primarily driven by As (32.8%), and the association with DBIL was primarily driven by Pb (30.9%). The associations between urinary metals and liver function might differ by sex and age. ConclusionUrinary metals were significantly associated with liver function parameters. Further studies are required to clarify the relationship between heavy metals and liver function.

P23-05: Urinary monohydroxyl-polycyclic aromatic hydrocarbons and metals in firefighters with active participation in controlled structure fires

P23-05: Urinary monohydroxyl-polycyclic aromatic hydrocarbons and metals in firefighters with active participation in controlled structure fires

Urinary essential and toxic metal mixtures, and type 2 diabetes mellitus: Telomere shortening as an intermediary factor?

The joint effect of metal mixtures on telomere function and type 2 diabetes mellitus (T2DM) is unclear. This large-scale cross-sectional study sought to assess the role of telomere length (TL) in the relationship between urinary essential and toxic metal mixtures, and T2DM in 7410 Chinese adults ≥ 60 years of age. Essential (Cr, Cu, Zn, Se) and non-essential metals (V, Al, Sb, Sn, Cd, Pb) in urine samples were quantified, while leukocyte TL was measured from blood samples. Restricted cubic splines regression showed nonlinear relationships between single metal and T2DM, and between TL and T2DM. Bayesian kernel machine regression and quantile-based g-computation showed that the overall status of urinary metals was positively associated with risk of developing T2DM, which was mainly explained by exposure to Pb, Cd, and Sb, excessive Se intake, and high excretion of Zn. Mediation analyses showed that shortened TL mediated 27.9% of the overall positive effect of metal exposure on T2DM, and this mediation was mainly explained by toxic metal exposure and excessive Se intake. Tobacco smoke exposure, extensive cooking at home, and black tea consumption were found to be important contributors of toxic metal exposures. Further studies are needed to explore the recommended Zn dosage for T2DM patients at different stages, which may ameliorate pancreatic senescence and glycemic progression.

Discovery of phytochelatins in human urine: Evidence for function in selenium disposition and protection against cadmium.

This report identifies, for the first time, a phytochelatin compound, phytochelatin 2 [γ-E-C-γ-E-C-G], and related metabolites in human urine. Phytochelatins are metal-binding peptides produced by plants. They are present in nearly all human diets, due to their ubiquity in plants. The urinary concentration of phytochelatin 2 among 143 adults was in the low micromolar range, and phytochelatin 2 and its metabolites had differential correlations with urinary selenium and toxic metals. Activities of ingested phytochelatins are largely undescribed. Observed urinary metal interactions were investigated further in cell and animal models. Selenite reacted with phytochelatin to form a phytochelatin selenotrisulfide, and the preformed selenotrisulfide showed increased selenium uptake by renal proximal tubule cells. In vivo studies further showed that oral phytochelatin increased renal selenium content and decreased lung cadmium in mice. Presence of phytochelatin in human urine combined with its function in selenium and heavy metal distribution present a new route by which diet may influence metal disposition and bioavailability.

Blood and Urinary Metal Levels among Exclusive Marijuana Users in NHANES (2005-2018).

Marijuana is the third most used drug in the world. Because the cannabis plant is a known scavenger of metals, we hypothesized that individuals who use marijuana will have higher metal biomarker levels compared with those who do not use. We combined data from the National Health and Nutrition Examination Survey (2005-2018) for participants, classified by use: non-marijuana/non-tobacco, exclusive marijuana, exclusive tobacco, and dual marijuana and tobacco use. Five metals were measured in blood and 16 in urine using inductively coupled plasma mass spectrometry; urinary metals were adjusted for urinary creatinine. Participants reporting exclusive marijuana use compared with non-marijuana/non-tobacco use had statistically significantly higher mean cadmium levels in blood [ (95% CI: 1.11, 1.34); ] and urine [ (95% CI: 1.0, 1.31); ] and statistically significantly higher mean lead levels in blood [ (95% CI: 1.07, 1.50); ] and urine [ (95% CI: , 1.50); ]. Our results suggest marijuana is a source of cadmium and lead exposure. Research regarding cannabis use and cannabis contaminants, particularly metals, should be conducted to address public health concerns related to the growing number of cannabis users. https://doi.org/10.1289/EHP12074.

Sex-specific associations between nine metal mixtures in urine and urine flow rate in US adults: NHANES 2009-2018.

The urinary system serves as a crucial pathway for eliminating metallic substances from the body, making it susceptible to the effects of metal exposure. However, limited research has explored the association between metal mixtures and bladder function. This study aims to investigate the relationship between urinary metal mixtures (specifically barium, cadmium, cobalt, cesium, molybdenum, lead, antimony, thallium, and tungsten) and urine flow rate (UFR) in the general population, utilizing multiple mixture analysis models. This study utilizes data obtained from the National Health and Nutrition Examination Survey. After adjusting for relevant covariates, we assessed the correlations between metal mixtures and UFR using three distinct analysis models: weighted quantile sum (WQS), quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR). Additionally, a gender-stratified analysis was conducted. Finally, we also performed sensitivity analyses. A total of 7,733 subjects were included in this study, with 49% being male. The WQS regression model, when fitted in the positive direction, did not yield any significant correlations in the overall population or in the male and female subgroups. However, when analyzed in the negative direction, the WQS index exhibited a negative correlation with UFR in the overall group (β = -0.078; 95% CI: -0.111, -0.045). Additionally, a significant negative correlation between the WQS index and UFR was observed in the female group (β = -0.108; 95% CI: -0.158, -0.059), while no significant correlation was found in the male group. The results obtained from the qgcomp regression model were consistent with those of the WQS regression model. Similarly, the BKMR regression model revealed a significant negative correlation trend between metal mixtures and UFR, with cadmium and antimony potentially playing key roles. Our study revealed a significant negative correlation between urinary metal mixture exposure and mean UFR in US adults, with notable gender differences. Specifically, higher urinary levels of cadmium and antimony were identified as potential key factors contributing to the decrease in mean UFR. These findings significantly contribute to the existing knowledge on the impact of metal mixtures on bladder function and provide valuable insights for safeguarding bladder health and preventing impaired bladder function.

Combined exposure to multiple metals on hypertension in NHANES under four statistical models.

Metals exposure has gained increasing attention in the hypertension prevention. However, previous studies have focused on the impacts of single or separated metals on hypertension, and the critical metals contributing to the prevalence of hypertension are still under discussion. We collected data from 5092 participants across three consecutive National Health and Nutrition Examination Survey (NHANES) circles (2011-2016). Weighted logistic regression, weighted quantile sum (WQS) regression, quantile-based g-computation (QGC), and Bayesian kernel machine regression (BKMR) analyses were conducted to evaluate the combined and individual effects of 15 urinary metals, as well as to identify the critical metals on the development of hypertension. In our study, the weighted prevalence of hypertension was 37.9%, and the average age was 47.42years. Manganese, uranium and tin were found as the independent risk factors for hypertension, while barium, lead, and thallium were found to have protective effects against hypertension. Lead, barium, tungsten, uranium, and tin were determined as critical elements for the prediction of hypertension. No significant interaction relationship was detected between multiple metals. There might be potential positive combined effects of urinary metal mixture on hypertension. Tungsten, uranium, and tin were positively associated with hypertension while lead and barium were negatively associated with hypertension. The underlying mechanisms of urinary metal exposure on the risk of hypertension deserve further investigations.

Correlation and interaction between urinary metals level and diabetes: A cross sectional study of community-dwelling elderly

Correlation and interaction between urinary metals level and diabetes: A cross sectional study of community-dwelling elderly

Independent and combined associations of urinary metals exposure with markers of liver injury: Results from the NHANES 2013–2016

BackgroundHeavy metals entering the human body could cause damage to a variety of organs. However, the combined harmful effects of exposure to various metals on liver function are not well understood. The purpose of the study was to investigate the independent and joint relationships between heavy metal exposure and liver function in adults. MethodsThe study involved 3589 adults from the National Health and Nutrition Examination Survey. Concentrations of urinary metals, including arsenic (As), cadmium (Cd), lead (Pb), antimony (Sb), barium (Ba), thallium (Tl), tungsten (W), uranium (U), were determined in urine using inductively coupled plasma mass spectrometry. Data for liver function biomarkers included alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transaminase (GGT), and alkaline phosphatase (ALP). Survey-weighted linear regression and quantile g-computation (qgcomp) were employed to evaluate the relationship of urinary metals with the markers of liver injury. ResultsCd, U and Ba were found to have positive correlations with ALT, AST, GGT, and ALP in the survey-weighted linear regression analyses. According to the qgcomp analyses, the total metal mixture was positively correlated with ALT (percent change: 8.15; 95% CI: 3.84, 12.64), AST (percent change: 5.55; 95% CI: 2.39, 8.82), GGT (percent change: 14.30; 95% CI: 7.81, 21.18), and ALP (percent change: 5.59; 95% CI: 2.65, 8.62), and Cd, U, and Ba were the main contributors to the combined effects. Positive joint effects were observed between Cd and U on ALT, AST, GGT and ALP, and U and Ba had positive joint effects on ALT, AST and GGT. ConclusionExposures to Cd, U, and Ba were individually associated with multiple markers of liver injury. Mixed metal exposure might be adversely correlated with markers of liver function. The findings indicated the potential harmful effect of metal exposure on liver function.

Application of mixture analysis methods in association between metals mixture exposure and DNA oxidative damage

Objectives: To study the association between metals mixture exposure and DNA oxidative damage using mixture analysis methods, and to explore the most significant exposure factors that cause DNA oxidative damage. Methods: Workers from steel enterprises were recruited in Shandong Province. Urinary metals were measured by using the inductively coupled plasma mass spectrometry method. The level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was determined by using the ultra-high performance liquid chromatography-mass spectrometry method. Bayesian kernel machine regression (BKMR), elastic net regression and quantile g-computation regression were used to analyze the association between urinary metals and urinary 8-OHdG. Results: A total of 768 subjects aged (36.15±7.40) years old were included in the study. BKMR, elastic net regression and quantile g-computation all revealed an overall positive association between the mixture concentration and increased urinary 8-OHdG. The quantile g-computation results showed that with a 25% increase in metal mixtures, the urinary 8-OHdG level increased by 77.60%. The elastic net regression showed that with a 25% increase in exposure risk score, the urinary 8-OHdG level increased by 26%. The BKMR summarized the contribution of individual exposures to the response, and selenium, zinc, and nickel were significant contributors to the urinary 8-OHdG elevation. Conclusion: Exposure to mixed metals causes elevated levels of DNA oxidative damage, and selenium, zinc, and nickel are significant exposure factors.

Human biomonitoring reference values, exposure distribution, and characteristics of metals in the general population of Taiwan: Taiwan environmental survey for Toxicants (TESTs), 2013-2016.

Human biomonitoring (HBM) provides information to identify chemicals that need to be assessed regarding potential health risks to human populations. We established a population-representative sample in Taiwan, namely the Taiwan Environmental Survey for Toxicants (TESTs) in 2013-2016. In total, 1871 participants (aged 7-97 years) were recruited from throughout Taiwan. A questionnaire survey was applied to obtain individuals' demographic characteristics, and urine samples were obtained to assess metal concentrations. Inductively coupled plasma-mass spectrometry was used to determine concentrations of urinary As (total), Cd, Co, Cr, Cu, Fe, Ga, In, Mn, Ni, Pb, Se, Sr, Tl, and Zn. The purpose of this study was to establish the human urinary reference levels (RVs) for metals in the general population of Taiwan. We found that median concentrations of urinary Cu, Fe, Pb, and Zn in males were statistically significant (p<0.05) higher than in females (Cu: 11.48vs. 10.00μg/L; Fe: 11.48 vs. 10.46μg/L; Pb: 0.87 vs. 0.76μg/L; and Zn: 448.93 vs. 348.35μg/L). On the contrary, Cd and Co were significantly lower in males than in females (Cd: 0.61 vs. 0.64μg/L; and Co: 0.27 vs. 0.40μg/L). Urinary Cd levels in the ≥18-year-old group (0.69μg/L) were significantly higher than those in the 7-17-year-old group (0.49μg/L, p<0.001). Among the investigated metals, most were significantly higher in the 7-17-year-old group than in the ≥18-year-old group, except for Cd, Ga, and Pb. Participants who lived in central Taiwan had higher median levels of urinary Cd, Cu, Ga, Ni, and Zn than those in other regions. Median levels of urinary As, Cd, Pb, and Se were significantly higher in participants who lived in harbor (94.12μg/L), suburban (0.68μg/L), industrial (0.92μg/L), and rural (50.29μg/L) areas, respectively, than the others who lived in other areas. RV95 percentiles of urinary metals (ng/mL) for 7-17/≥18-year-old groups were As (346.9/370.0), Cd (1.41/2.21), Co (2.30/1.73), Cr (0.88/0.88), Cu (28.02/22.78), Fe (42.27/42.36), Ga (0.13/0.12), In (0.05/0.04), Mn (3.83/2.91), Ni (8.09/6.17), Pb (8.09/5.75), Se (122.4/101.9), Sr (556.5/451.3), Tl (0.57/0.49), and Zn (1314.6/1058.8). In this study, we have highlighted the importance of As, Cd, Pb, and Mn exposure in the general population of Taiwan. The established RV95 of urinary metals in Taiwanese would be fundamental information to promote the reduction of metal exposure or policy intervention. We concluded that urinary levels of exposure to certain metals in the general Taiwanese population varied by sex, age, region, and urbanization level. References of metal exposure in Taiwan were established in the current study.

Association between mediterranean diet and metal(loid) exposure in 4-5-year-old children living in Spain.

Even relatively low levels of metals exposure may impact health, particularly among vulnerable populations such as infants and young children. However, little is known about the interplay between simultaneous metal exposures, common in real-life scenarios, and their association with specific dietary patterns. In this study, we have evaluated the association between adherence to Mediterranean diet (MD) and urinary metal concentrations individually and as an exposure mixture in 713 children aged 4-5-years from the INMA cohort study. We used a validated food frequency questionnaire to calculate two MD indexes scores: aMED and rMED. These indexes gather information on various food groups within the MD and score differently. To measure urinary concentrations of cobalt, copper, zinc, molybdenum, selenium, lead, and cadmium as exposure biomarkers, we used inductively coupled plasma mass spectrometry (ICP-MS), coupled with an ion chromatography (IC) equipment for arsenic speciation analysis. We applied linear regression and quantile g-computation, adjusted for confounders, to analyse the association between MD adherence and exposure to the metal mixture. High adherence to MD such as the quintile (Q) 5 MD was associated with higher urinary arsenobetaine (AsB) levels than Q1, with β values of 0.55 (confidence interval - CI 95% 0.01; 1.09) for aMED and 0.73 (CI 95% 0.13; 1.33) for rMED. Consumption of fish was associated with increased urinary AsB but reduced inorganic arsenic concentrations. In contrast, the aMED vegetables consumption increased urinary inorganic arsenic content. A moderate level of adherence to MD (Q2 and Q3) was associated with lower copper urinary concentrations than Q1, with β values of −0.42 (CI 95% −0.72; −0.11) for Q2 and -0.33 (CI 95% −0.63; −0.02) for Q3, but only with aMED. Our study, conducted in Spain, revealed that adhering to the MD reduces exposure to certain metals while increasing exposure to others. Specifically, we observed increase in exposure to non-toxic AsB, highlighting the significance of consuming fish/seafood. However, it is crucial to emphasize the necessity for additional efforts in reducing early-life exposure to toxic metals, even when adhering to certain food components of the MD.

Short-term exposure to multiple metals mixture and mitochondrial DNA copy number among children: A panel study

BackgroundLittle is known regarding the individual and overall associations of short-term co-exposure to metals mixture with mitochondrial DNA copy number (mtDNAcn) among healthy children. MethodsWe conducted a panel study across three seasons among 144 children aged 4 to 12 years in Guangzhou. For each season, we collected the first-morning urine for four consecutive days and fasting blood on the 4th day to detect 23 urinary metals and blood leukocyte mtDNAcn, respectively. Linear mixed-effect (LME) models and multiple informant models were used to examine the relations of individual metals with mtDNAcn over different lag days, and the least absolute shrinkage and selection operator (LASSO) regression was applied to determine the most important metal. We further employed weighted quantile sum (WQS) regression to investigate the overall association of metals mixture with mtDNAcn. ResultsNickel (Ni), manganese (Mn) and antimony (Sb) were independently associated with mtDNAcn in a linear dose-response manner. Each 1-fold increase in Ni at lag 0 day, Mn and Sb at lag 2 day was associated with respective decrements of 8.74 %, 6.93 % and 3.98 % in mtDNAcn in multi-metal LME models. LASSO regression also selected Ni, Mn and Sb as the most significant metals at the corresponding lag day. WQS regression showed overall inverse associations between metals mixture and mtDNAcn both at lag 0 and lag 2 day, with mtDNAcn decreased by 2.75 % and 3.14 % in response to a quartile increase in the WQS index. Additionally, the associations of Ni and Mn with decreased mtDNAcn were stronger among children younger than 7 years, girls and those having less vegetables and fruit intake. ConclusionWe found an overall association between metals mixture and decreased mtDNAcn among healthy children, in which Ni, Mn and Sb were the major contributors. Younger children, girls and those with less vegetables and fruit intake were more susceptible.

Metal mixtures and DNA methylation measures of biological aging in American Indian populations

IntroductionNative American communities suffer disproportionately from elevated metal exposures and increased risk for cardiovascular diseases and diabetes. DNA methylation is a sensitive biomarker of aging-related processes and novel epigenetic-based “clocks” can be used to estimate accelerated biological aging that may underlie increased risk. Metals alter DNA methylation, yet little is known about their individual and combined impact on epigenetic age acceleration. Our objective was to investigate the associations of metals on several DNA methylation-based aging measures in the Strong Heart Study (SHS) cohort. MethodsBlood DNA methylation data from 2,301 SHS participants was used to calculate age acceleration of epigenetic clocks (PhenoAge, GrimAge, DunedinPACE, Hannum, Horvath). Urinary metals [arsenic (As), cadmium (Cd), tungsten (W), zinc (Zn), selenium (Se), molybdenum (Mo)] were creatinine-adjusted and categorized into quartiles. We examined associations of individual metals through linear regression models and used Bayesian Kernel Machine Regression (BKMR) for the impact of the total metal mixture on epigenetic age acceleration. ResultsThe mixture of nonessential metals (W, As, Cd) was associated with greater GrimAge acceleration and DunedinPACE, while the essential metal mixture (Se, Zn, Mo) was associated with lower epigenetic age acceleration. Cd was associated with increased epigenetic age acceleration across all clocks and BKMR analysis suggested nonlinear associations between Se and DunedinPACE, GrimAge, and PhenoAge acceleration. No interactions between individual metals were observed. The associations between Cd, Zn, and epigenetic age acceleration were greater in never smokers in comparison to current/former smokers. ConclusionNonessential metals were positively associated with greater epigenetic age acceleration, with strongest associations observed between Cd and DunedinPACE and GrimAge acceleration. In contrast, essential metals were associated with lower epigenetic aging. Examining the influence of metal mixtures on epigenetic age acceleration can provide insight into metals and aging-related diseases.

Maternal urinary metal(loid)s and risk of preterm birth: A cohort study in the Tibetan Plateau

Maternal metal(loid)s exposure has been related to preterm birth (PTB), but the results are still inconclusive. Previous studies have mainly discussed the harmful metal(loid)s, neglecting beneficial ones. We examined the association of maternal metal(loid)s with PTB and gestational age (GA) in a birth cohort from the Tibetan Plateau. We measured 29 metal(loid)s in urine samples from 1081 pregnant women in the third trimester. Information regarding demographics, socioeconomic status, diet, medication, and lifestyle was collected through standardized interviews. The associations of single metal(loid)s with PTB or GA were evaluated using a generalized linear mixed-effects model or linear mixed-effects model. Elastic net and Bayesian kernel machine regressions were used to explore the joint associations. Magnesium (Mg), Copper (Cu), and Tin (Sn) were the main “harmful” metal(loid)s positively and negatively associated with PTB or GA, respectively. Mg was the dominant “harmful” metal(loid)s associated with PTB in a J-shape. A one-fold increase in Mg was associated with a 38% increased risk of PTB [OR (95% CI) = 1.38 (1.15, 1.65), PFDR＜0.05] and 0.17 weeks shortening of GA [β (95% CI) = −0.25 (−0.35, −0.14), PFDR＜0.05]. Cesium (Cs), rubidium (Rb), and Molybdenum (Mo) were the main “beneficial” metals. Cs dominated the “beneficial” associations and was negatively associated with PTB in a linear manner. A one-fold increase in Cs was associated with a 67% decreased risk of PTB [OR (95% CI) = 0.43 (0.27, 0.67), PFDR＜0.05] and 0.24 weeks of prolonged GA [β (95% CI) = 0.35 (0.13, 0.56), PFDR＜0.05]. Ethnicity and living altitude modified the association of Mg and Cu with PTB or GA. In conclusion, Maternal urinary metal(loid)s were bi-directionally associated with PTB in a population in the Tibetan Plateau. Mg and Cs were the dominant “harmful” and “beneficial” metal(loid)s, respectively.