Association between Multiple Trace Elements, Executive Function, and Cognitive Impairment with No Dementia in Older Adults.

Many studies suggest a significant association between individual essential trace elements (ETEs) and cognitive impairment in older adults, but evidence of the synchronized effect of multiple ETEs on cognitive function is lacking. We investigated the association between multiple ETEs, cognitive impairment with no dementia (CIND), and executive function in older Korean adults, using the Bayesian kernel machine regression (BKMR) model. Three hundred and thirty-six older adults were included as the study population and classified as the CIND and control groups. Blood manganese (Mn), copper (Cu), zinc (Zn), selenium (Se), and molybdenum (Mo) were measured as relevant ETEs. The frontal/executive tests included digit symbol coding (DSC), the Korean color word Stroop test (K-CWST), a controlled oral word association test (COWAT), and a trial-making test (TMT). Overall, the BKMR showed a negative association between multiple ETEs and the odds of CIND. Mn was designated as the most dominant element associated with the CIND (PIP = 0.6184), with a U-shaped relationship. Cu and Se levels were positively associated with the K-CWST percentiles (ß = 31.78; 95% CI: 13.51, 50.06) and DSC percentiles (ß = 25.10; 95% CI: 7.66, 42.53), respectively. Our results suggest that exposure to multiple ETEs may be linked to a protective mechanism against cognitive impairment in older adults.

Associations Between Individual and Combined Metal Exposures in Whole Blood and Kidney Function in U.S. Adults Aged 40 Years and Older.

The effects of metal exposure on kidney function have been reported in previous literature. There is limited and inconsistent information on the associations between individual and combined exposures to metals and kidney function among the middle-aged and older population. The aim of this study was to clarify the associations of exposure to individual metals with kidney function while accounting for potential coexposure to metal mixtures and to evaluate the joint and interactive associations of blood metals with kidney function. A total of 1669 adults aged 40 years and older were enrolled in the present cross-sectional study using the 2015-2016 National Health and Nutrition Examination Survey (NHANES). Single-metal and multimetal multivariable logistic regression models, quantile G-computation, and Bayesian kernel machine regression models (BKMR) were fitted to explore the individual and joint associations of whole blood metals [lead (Pb), cadmium (Cd), mercury (Hg), cobalt (Co), manganese (Mn), and selenium (Se)] with the odds of decreased estimated glomerular filtration rate (eGFR) and albuminuria. A decreased eGFR was defined as an eGFR ≤ 60 mL/min per 1.73 m2, and albuminuria was categorized as a urinary albumin-creatinine ratio (UACR) of ≥ 30.0 mg/g. The results from quantile G-computation and BKMR indicated positive associations between exposure to the metal mixture and the prevalence of decreased eGFR and albuminuria (all P values < 0.05). These positive associations were mainly driven by blood Co, Cd, and Pb. Furthermore, blood Mn was identified as an influential element contributing to an inverse correlation with kidney dysfunction within metal mixtures. Increasing blood Se levels were negatively associated with the prevalence of decreased eGFR and positively associated with albuminuria. In addition, a potential pairwise interaction between Mn-Co on decreased eGFR was identified by BKMR analysis. Findings from our study suggested a positive association between exposure to the whole blood metal mixture and decreased kidney function, with blood Co, Pb, and Cd being the main contributors to this association, while Mn demonstrated an inverse relationship with renal dysfunction. However, as our study was cross-sectional in nature, further prospective studies are warranted to better understand the individual and combined effects of metals on kidney 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 47.42 years. 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.

The association between the essential metal mixture and fasting plasma glucose in Chinese community-dwelling elderly people.

BACKGROUND: Epidemiological studies about the effect of essential metal mixture on fasting plasma glucose (FPG) levels among elderly people are sparse. The object of this study was to examine the associations of single essential metals and essential metal mixture with FPG levels in Chinese community-dwelling elderly people. METHODS: The study recruited 2348 community-dwelling elderly people in total. Inductively coupled plasma-mass spectrometry was adopted to detect the levels of vanadium (V), selenium (Se), magnesium (Mg), cobalt (Co), calcium (Ca), and molybdenum (Mo) in urine. The relationships between single essential metals and essential metal mixture and FPG levels were evaluated by linear regression and Bayesian kernel machine regression (BKMR) models, respectively. RESULTS: In multiple-metal linear regression models, urine V and Mg were negatively related to the FPG levels (ß = - 0.016, 95 % CI: - 0.030 to - 0.003 for V; ß = - 0.021, 95 % CI: - 0.033 to - 0.009 for Mg), and urine Se was positively related to the FPG levels (ß = 0.024, 95 % CI: 0.014-0.034). In BKMR model, the significant relationships of Se and Mg with the FPG levels were also found. The essential metal mixture was negatively associated with FPG levels in a dose-response pattern, and Mg had the maximum posterior inclusion probability (PIP) value (PIP = 1.0000), followed by Se (PIP = 0.9968). Besides, Co showed a significant association with decreased FPG levels in older adults without hyperlipemia and in women. CONCLUSIONS: Both Mg and Se were associated with FPG levels, individually and as a mixture. The essential metal mixture displayed a linear dose-response relationship with reduced FPG levels, with Mg having the largest contribution to FPG levels, followed by Se. Further prospective investigations are necessary to validate these exploratory findings.

Associations of metal mixtures in the meconium with birth outcomes in northern Taiwan.

Previous studies investigated prenatal exposure to neurotoxic metals in relation to birth anthropometrics. However, limited information has been developed on associations with birth outcomes of fetal exposure to metal mixtures using the meconium as a biomarker. The purpose of this study was to evaluate relationships of the combined effects of mercury (Hg), lead (Pb), cadmium (Cd), and arsenic (As) concentrations in the meconium on birth outcomes (i.e., birth weight, birth length, and head circumference). This cross-sectional study was conducted in northern Taiwan between January 2007 and December 2009. We collected 526 meconium samples within the first 24 h after birth to measure the in utero mixed-metal exposure determined using inductively coupled plasma/mass spectrometry (ICP-MS). We used a multivariable regression and Bayesian kernel machine regression (BKMR) to estimate associations of the combined effects and identify important mixture components with growth impairments. Our results revealed Hg, Pb, Cd, and As concentrations in the meconium and enhanced the quantity of research on meconium analyses. The overall effects of Hg, Pb, Cd, and As concentrations in the meconium as prenatal exposure biomarkers were negatively associated with birth growth. Fetal exposure to Hg and Pb was correlated with decreased birth weights. Hg and Pb concentrations in the meconium were linearly inversely related to the birth weight, birth length, and head circumference. Effects of fetal exposure to As and Cd on birth outcomes were not obvious. A significant increasing relationship was detected between Hg concentrations in the meconium and maternal fish consumption during pregnancy. Higher Pb concentrations in the meconium were observed among infants of mothers who consumed Chinese herbal medicines. Reducing maternal fish consumption and Chinese herbal medicine consumption during pregnancy could limit infant exposure to metals.

Manganese, iron, copper, and selenium co-exposure and osteoporosis risk in Chinese adults.

BACKGROUND & AIMS: Previous experimental studies demonstrated that either deficient or excessive trace elements, such as manganese (Mn), iron (Fe), copper (Cu) and selenium (Se), are detrimental to bone health. Epidemiologic evidence for the effect of the four trace elements on osteoporosis (OP) risk remains inadequate. This cross-sectional study aimed to examine their associations with the OP risk among Chinese adults. METHODS: Concentrations of Mn, Fe, Cu, and Se were measured in plasma using an inductively coupled plasma mass spectrometer among 627 Chinese adults aged ≥ 50 years. Individual effect of the four elements on OP risk was analyzed by logistic regression and Bayesian Kernel Machine Regression (BKMR) models. The latter model was also adopted to examine the exposure-response relationships and joint effects of the four elements on OP risk. RESULTS: The median Mn, Fe, Cu, and Se levels were 4.78, 1026.63, 904.55, and 105.39 µg/L, respectively, in all participants. Inverse associations of Fe and Se levels with OP risk were observed in the logistic regression model. BKMR analysis revealed a U-shape pattern for the Fe-OP association, and a reduced OP risk in response to co-exposure of the four elements above the 50th percentiles but an elevated one in response to that below the 50th percentiles. Sex discrepancy existed in the findings. No interactions were found for the four elements affecting OP risk. CONCLUSIONS: Co-exposure to Mn, Fe, Cu, and Se was associated with improved bone density, where Fe contributed most to the beneficial effect. Further studies are needed to verify these findings and explore the underlying biological mechanism.

Identifying Effects of Urinary Metals on Type 2 Diabetes in U.S. Adults: Cross-Sectional Analysis of National Health and Nutrition Examination Survey 2011-2016.

Growing evidence supports the associations of metal exposures with risk of type 2 diabetes (T2D), but the methodological limitations overlook the complexity of relationships within the metal mixtures. We identified and estimated the single and combined effects of urinary metals and their interactions with prevalence of T2D among 3078 participants in the NHANES 2011-2016. We analyzed 15 urinary metals and identified eight metals by elastic-net regression model for further analysis of the prevalence of T2D. Bayesian kernel machine regression and the weighted quantile sum (WQS) regression models identified four metals that had greater importance in T2D, namely cobalt (Co), tin (Sn), uranium (U) and strontium (Sr). The overall OR of T2D was 1.05 (95% CI: 1.01-1.08) for the positive effects and 1.00 (95% CI: 0.98-1.02) for the negative effect in the WQS models. We observed positive (Poverall = 0.008 and Pnon-linear = 0.100 for Co, Poverall = 0.011 and Pnon-linear = 0.138 for Sn) and inverse (Poverall = 0.001, Pnon-linear = 0.209 for Sr) linear dose-response relationships with T2D by restricted cubic spline analysis. Both additive and multiplicative interactions were found in urinary Sn and Sr. In conclusion, urinary Co, Sn, U and Sr played important roles in the development of T2D. The levels of Sn might modify the effect of Sr on T2D risk.

Do urinary metals associate with the homeostasis of inflammatory mediators? Results from the perspective of inflammatory signaling in middle-aged and older adults.

OBJECTIVE: We aimed to investigate whether urinary metal mixtures are associated with the homeostasis of inflammatory mediators in middle-aged and older adults. METHODS: A four-visit repeated-measures study was conducted with 98 middle-aged and older adults from five communities in Beijing, China. Only one person was lost to follow-up at the third visit. Ultimately, 391 observations were included in the analysis. The urinary concentrations of 10 metals were measured at each visit using inductively coupled plasma mass spectrometry (ICP-MS) with a limit of detection (LOD) ranging from 0.002 to 0.173 µg/L, and the detection rates were all above 84%. Similarly, 14 serum inflammatory mediators were measured using a Beckman Coulter analyzer and the Bio-Plex MAGPIX system. A linear mixed model (LMM), LMM with least absolute shrinkage and selection operator regularization (LMMLASSO), and Bayesian kernel machine regression (BKMR) were adopted to explore the effects of urinary metal mixtures on inflammatory mediators. RESULTS: In LMM, a two-fold increase in urinary cesium (Cs) and chromium (Cr) was statistically associated with -35.22% (95% confidence interval [CI]: -53.17, -10.40) changes in interleukin 6 (IL-6) and -11.13% (95 %CI: -20.67, -0.44) in IL-8. Urinary copper (Cu) and selenium (Se) was statistically associated with IL-6 (88.10%, 95%CI: 34.92, 162.24) and tumor necrosis factor-alpha (TNF-α) (22.32%, 95%CI: 3.28, 44.12), respectively. Similar results were observed for the LMMLASSO and BKMR. Furthermore, Cr, Cs, Cu, and Se were significantly associated with other inflammatory regulatory network mediators. For example, urinary Cs was statistically associated with endothelin-1, and Cr was statistically associated with endothelin-1 and intercellular adhesion molecule 1 (ICAM-1). Finally, the interaction effects of Cu with various metals on inflammatory mediators were observed. CONCLUSION: Our findings suggest that Cr, Cs, Cu, and Se may disrupt the homeostasis of inflammatory mediators, providing insight into the potential pathophysiological mechanisms of metal mixtures and chronic diseases.

Exposure to multiple trace elements and miscarriage during early pregnancy: A mixtures approach.

BACKGROUND: Exposure to some conventional trace elements has been found to be associated with miscarriage; however, evidence for combined exposure is inconclusive. Therefore, it is important to explore the joint associations between toxic and essential trace elements and miscarriage. METHODS: This cross-sectional study measured a wide range of element levels in the whole blood of pregnant women by using inductively coupled plasma mass spectrometry. The associations between individual elements and miscarriage were appraised using logistic regression model. Multi-exposure models, including Bayesian kernel machine regression (BKMR) and weighted quantile sum regression (WQS), were used to explore the mixed exposure to elements. Furthermore, grouped weighted quantile sum (GWQS) considered multiple elements with different magnitudes and directions of associations. RESULTS: In logistic regression, the odds ratios (ORs) with a 95% confidence interval (CI) in the highest quartiles were 5.45 (2.00, 15.91) for barium, 0.28 (0.09, 0.76) for copper, and 0.32 (0.12, 0.83) for rubidium. These exposure-outcome associations were confirmed and supplemented by BKMR, which indicated a positive association for barium and negative associations for copper and rubidium. In WQS, a positive association was found between mixed elements and miscarriage (OR: 1.71; 95% CI: 1.07, 2.78), in which barium (75.7%) was the highest weighted element. The results of GWQS showed that the toxic trace element group dominated by barium was significantly associated with increased ORs (OR: 2.71; 95% CI: 1.74, 4.38). Additionally, a negative association was observed between the essential trace element group and miscarriage (OR: 0.32; 95% CI: 0.18, 0.54), with rubidium contributing the most to the result. CONCLUSIONS: As a toxic trace element, barium was positively associated with miscarriage both by individual and multiple evaluations, while essential trace elements, particularly rubidium and copper, exhibited negative associations. Our findings provide significant evidence for exploring the effects of trace elements on miscarriage.