Metabolic profiling detects early effects of environmental and lifestyle exposure to cadmium in a human population

High-resolution 1H NMR spectroscopy (metabonomics) was used to acquire urinary metabolic profiles from 178 human volunteers. The spectral data were subjected to multivariate and univariate analysis to identify metabolites that were correlated with lifestyle or biological factors. Urinary levels of 8-oxo-deoxyguanosine were also measured, using mass spectrometry, as a marker of systemic oxidative stress.Six urinary metabolites, either associated with mitochondrial metabolism (citrate, 3-hydroxyisovalerate, 4-deoxy-erythronic acid) or one-carbon metabolism (dimethylglycine, creatinine, creatine), were associated with cadmium exposure. In particular, citrate levels retained a significant correlation to urinary cadmium and smoking status after controlling for age and sex. Oxidative stress (as determined by urinary 8-oxo-deoxyguanosine levels) was elevated in individuals with high cadmium exposure, supporting the hypothesis that heavy metal accumulation was causing mitochondrial dysfunction.This study shows evidence that an NMR-based metabolic profiling study in an uncontrolled human population is capable of identifying intermediate biomarkers of response to toxicants at true environmental concentrations, paving the way for exposome research.From the point of conception and throughout life, humans experience a broad range of physical, chemical and biological exposures. The health effects of such exposures will depend not only on dose but also on their interaction with each other and with the characteristics of the individual, such as age, sex and genotype. Hence, it is a persistent and significant challenge to understand how specific environmental factors produce effects on human health. Biomarkers already play an important role in characterizing both dose and effect; however, their full potential remains to be explored. Molecular profiling technologies ('-omics') have been suggested to be an important route to the discovery of novel biomarkers to improve exposure assess