Association of Urinary Phthalate Metabolites with Lipid Profiles and the Mediating Role of Serum Globulin: A Repeated-Measures Study

The relationship between exposure to multiple phthalates and blood lipid levels, along with underlying mechanisms, remains unclear. We conducted a panel study with 119 adults, each participating in three visits across different seasons, to evaluate associations between phthalate mixture and lipid profiles, as well as the mediating effect of serum globulin. Ten urinary phthalate metabolites (mPAEs) were measured over four consecutive days each season. Linear mixed-effect models, Bayesian kernel machine regression (BKMR), and Bayesian weighted quantile sum (BWQS) regression were used to explore associations between mPAEs and lipid levels. Several mPAEs were significantly associated with elevated total cholesterol (TC) at a one-day lag and low-density lipoprotein cholesterol (LDL-C) on the same day. These associations were more pronounced in males and individuals with abdominal obesity. Consistent with BWQS results, BKMR analysis indicated that LDL-C levels increased with higher exposure to mPAE mixture, with a percentage change of 2.45% (95% confidence interval [CI]: 0.18, 4.78) for ten mPAEs and 2.29% (95% CI: 0.51, 4.10) for four low-molecular-weight phthalates, primarily driven by Mono-methyl phthalate (MMP). Higher TC levels were associated with the mPAE mixture (1.31%, 95% CI: 0.36, 2.27) and high-molecular-weight phthalate mixture (1.25%, 95% CI: 0.37, 2.14), driven by mono-(2-ethyl-5-carboxypentyl) phthalate and mono-ethyl phthalate. Serum globulin mediated the relationship between MMP and TC, accounting for 35.8% of the mediation effect. Exposure to mPAEs, individually or in mixture, is associated with increased LDL-C and TC levels, with serum globulin potentially mediating the increase in TC levels related to MMP exposure.