Total blood mercury, plasma homocysteine, methylmalonic acid and folate in US children aged 3-5years, NHANES 1999-2004

Background: Mercury is a known neurotoxicant; however, the relationship between childhood exposures and neurodevelopmental outcomes is uncertain, and may be modified by nutrition-related susceptibilities. In vitro studies found that mercury inhibited methionine synthase, an enzyme that interacts with vitamin B-12 and folate to regenerate the amino acid methionine from homocysteine, and inhibition of methionine synthase diverted homocysteine to cysteine and glutathione synthesis. The relationships between mercury, homocysteine, B-12, and folate have not been examined in children. Objective: This study aimed to evaluate associations between Hg and homocysteine in male and female children differentiated by higher and lower methylmalonic acid (MMA, an indicator of vitamin B-12 deficiency) and folate status. Design: Cross-sectional data on total blood mercury (Hg), plasma homocysteine, MMA, and serum folate were obtained from the 1999-2004 National Health and Nutrition Examination Surveys for children aged 3-5. years (n = 1005). We used multiple linear regression to evaluate relationships between homocysteine and Hg quartiles, stratified by sex, MMA ≥ and folate < sample medians, adjusted for demographic, anthropometric, and environmental factors. Results: In boys with higher MMA and lower folate (n = 135), but not in other children, we observed inverse associations between homocysteine and Hg. Children with Hg > 3.49 μmol/L showed 1.14 μmol/L lower homocysteine (p < 0.001) relative to the lowest quartile (≤ 0.70 μmol/L) {p-value for trend < 0.001}. Compared to other subsamples, this subsample had significantly higher homocysteine levels. Conclusion: Hg was inversely correlated with plasma homocysteine in young boys, but not girls, with higher MMA and lower folate. Additional studies are merited to evaluate Hg and amino acid metabolism in susceptible children.