Metabolomic Signatures of Lead Exposure in the VA Normative Aging Study

Abstract Background Lead (Pb) is widespread and exposure to this non-essential heavy metal can cause multiple negative health effects; however the mechanisms underlying these effects remain incompletely understood. Objectives To identify plasma metabolomic signatures of Pb exposure, as measured in blood and toenails. Methods In a subset of men from the VA Normative Aging Study, mass-spectrometry based plasma metabolomic profiling was performed. Pb levels were measured in blood samples and toenail clippings collected concurrently. Multivariable linear regression models, smoothing splines and Pathway analyses were employed to identify metabolites associated with Pb exposure. Results In 399 men, 858 metabolites were measured and passed QC, of which 154 (17.9%) were significantly associated with blood Pb (p Discussion Pb exposure is responsible for 0.6% of the global burden of disease and metabolomics is particularly well-suited to explore its pathogenic mechanisms. In this study, we identified metabolites and metabolomic pathways associated with Pb exposure that suggest that Pb exposure acts through oxidative stress and immune dysfunction. These findings help us to better understand the biology of this important public health burden.