Abstract
BACKGROUND: Exposure to environmental metals has been increasingly associated with systemic inflammation, which is implicated in the pathogenesis of various chronic diseases, including those with neurodegenerative aspects. However, the complexity of exposure and response relationships, particularly for mixtures of metals, has not been fully elucidated. OBJECTIVE: This study aims to assess the individual and combined effects of lead, cadmium, and mercury exposure on systemic inflammation as measured by C-reactive protein (CRP) levels, using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018. METHODS: We employed Bayesian Kernel Machine Regression (BKMR) to analyze the NHANES 2017-2018 data, allowing for the evaluation of non-linear exposure-response functions and interactions between metals. Posterior Inclusion Probabilities (PIP) were calculated to determine the significance of each metal's contribution to CRP levels. RESULTS: The PIP results highlighted mercury's significant contribution to CRP levels (PIP = 1.000), followed by cadmium (PIP = 0.6456) and lead (PIP = 0.3528). Group PIP values confirmed the importance of considering the metals as a collective group in relation to CRP levels. Our BKMR analysis revealed non-linear relationships between metal exposures and CRP levels. Univariate analysis showed a flat relationship between lead and CRP, with cadmium having a positive relationship. Mercury exhibited a U-shaped association, indicating both low and high exposures as potential risk factors for increased inflammation. Bivariate analysis confirmed this relationship when contaminants were combined with lead and cadmium. Analysis of single-variable effects suggested that cadmium and lead are associated with higher values of the h function, a flexible function that takes multiple metals and combines them in a way that captures the complex and potentially nonlinear relationship between the metals and CRP. The overall exposure effect of all metals on CRP revealed that exposures below the 50th percentile exposure level are associated with an increase in CRP levels, while exposures above the 60th percentile are linked to a decrease in CRP levels. CONCLUSIONS: Our findings suggest that exposure to environmental metals, particularly mercury, is associated with systemic inflammation. These results highlight the need for public health strategies that address the cumulative effects of metal exposure and reinforce the importance of using advanced statistical methods to understand the health impact of environmental contaminants. Future research should focus on the mechanistic pathways of metal-induced inflammation and longitudinal studies to ascertain the long-term effects of these exposures.