Vitamin D (VD) plays an important role in maintaining musculoskeletal health, redox homeostasis, and the immune system, and are commonly dysregulated by endocrine disrupting chemicals, especially phthalates and bisphenol A (BPA). It is considered that continuous exposure to phthalates and BPA would change the endogenous metabolite profiles associated with anti-oxidant activity of VD, but no exact metabolites have yet been identified. Therefore, we performed this study to find the endogenous metabolites altered by phthalates and BPA exposure using untargeted metabolic profiling and to investigate the role of metabolites in the inhibitory mechanism on the anti-oxidant activity of VD.

Plasma metabolic profiling based on the liquid chromatography-mass spectrometry was performed in the two groups: severe deficiency of 25-hydroxyvitamin D (25(OH)D) and low exposure to phthalates and BPA; and deficiency of 25(OH)D and high exposure to phthalates and BPA. Multivariate analysis showed a distinct separation between two groups, and a total of eight metabolites were annotated, and three were statistically significant: lysophosphatidylcholine (lysoPC) 18:0, platelet activating factor (PAF) C16, and 11Z-eicosenamide. Plasma levels of lysoPC 18:0 or PAF C16 were elevated in the group with severe deficiency of 25(OH)D and high exposure to phthalates and BPA (p=0.014) and achieved an AUC of 0.769 (95% CI: 0.632–0.883) with accuracy of 74.4% in receiver operating characteristic curve analysis. These metabolites are generated as byproducts by lipid peroxidation and estimated to be involved in the network that interferes with the anti-oxidant activity of VD upon exposure to phthalates and BPA. This study results provide useful information on how the anti-oxidant activity of VD is disturbed upon exposure to phthalates and BPA.