Association between bisphenol A exposure, methylmalonic acid, and cardiovascular disease among adults aged 60 and younger.

BACKGROUND: Methylmalonic acid (MMA) has been associated with genetic factors and vitamin B12 status. However, the impact of environmental pollutant exposure on MMA levels and whether MMA statistically accounts for a portion of the pollutant-cardiovascular disease (CVD) risk remain unexplored. AIM: To assess the association between bisphenol A (BPA) and MMA and quantify the extent to which MMA accounts for the BPA-CVD association among adults aged 60 and younger. METHODS: Cross-sectional data from 2275 adults aged ≤ 60 years were obtained from the US National Health and Nutrition Examination Survey (NHANES). Linear regression analyses and restricted cubic spline regression were employed to assess the association between BPA and MMA, and network toxicology analyses were utilized to explore the potential mechanisms underlying the BPA-MMA relationship. Mediation analyses were used to decompose the total BPA-CVD association into direct and MMA-mediated indirect components. RESULTS: BPA was significantly and positively associated with MMA, independent of vitamin B12 levels (β=0.04; 95% CI: 0.01, 0.06). A total of 1124 potential target genes linked to BPA's impact on mitochondria were identified, with significant enrichment in the "propionate metabolism" pathway (hsa00640). Furthermore, the indirect association through MMA accounted for 4.41% (P < 0.001) of the total BPA-CVD association. CONCLUSION: Among adults aged 60 and younger, BPA exposure is associated with increased MMA, and MMA accounts for a modest proportion of the BPA-CVD association.