Mercury, homocysteine, methylmalonic acid and folate in US children aged 3-5 years, NHANES 1999-2004

Mercury is a known neurotoxicant; however, associations between exposures and neurodevelopment are inconsistent, and may be modified by nutritional 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 production. This study aimed to evaluate associations between total blood mercury (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. Cross-sectional data on 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 age, body mass index, blood cadmium, lead and cotinine, and 30-day beneficial fish intake. In boys with higher MMA and lower folate (n=135), but not in other children, we observed inverse associations between Hg and homocysteine. Children with Hg>3.49 µmol/L showed 1.27 µmol/L lower homocysteine (95% Confidence Interval=-1.91, -0.63) relative to the lowest Hg quartile (<=.70 µmol/L) {p-value for trend=0.002; R2=.30}. Compared to children without both higher MMA and lower folate, this subsample had significantly higher homocysteine levels. Compared to girls, this subsample had significantly lower Hg levels. In summary, Hg was inversely correlated with plasma homocysteine in young boys with higher MMA and lower folate. Research is merited to evaluate Hg and amino acid metabolism in susceptible children.