Folate, Cobalamin, Cysteine, Homocysteine, and Arsenic Metabolism among Children in Bangladesh

Megan N. Hall, Xinhua Liu, Vesna Slavkovich, Vesna Ilievski, J. Richard Pilsner, Shafiul Alam, Pam Factor-Litvak, Joseph H. Graziano, and Mary V. Gamble

Background: Approximately 35 million people in Bangladesh are chronically exposed to inorganic arsenic (InAs) in drinking water. Methylation of InAs to monomethylarsonic (MMA) and dimethylarsinic acids (DMA) relies on folate-dependent one-carbon metabolism and facilitates urinary arsenic (uAs) elimination.

Objectives: We examined the relationships between folate, cobalamin, cysteine, total homocysteine (tHcys), and uAs metabolites in a sample of 6-year-old Bangladeshi children (n = 165).

Methods: Children provided blood samples for measurement of tHcys, folate, cobalamin, and cysteine, and urine specimens for the measurement of total uAs and As metabolites.

Results: Consistent with our studies in adults, mean tHcys concentrations (7.9 μmol/L) were higher than those reported among children of similar ages in other populations. Nineteen percent of the children had plasma folate concentrations < 9.0 nmol/L. The proportion of total uAs excreted as InAs (%InAs) was inversely correlated with folate (r = –0.20, p = 0.01) and cysteine (r = –0.23, p = 0.003), whereas the correlations between %DMA and both folate (r = 0.12, p = 0.14) and cysteine (r = 0.11, p = 0.15) were positive. Homocysteine was inversely correlated (r = –0.27, p = 0.009) with %MMA in males, and the correlation with %DMA was positive (r = 0.13, p = 0.10).

Conclusions: These findings suggest that, similar to adults, folate and cysteine facilitate As methylation in children. However, the inverse correlation between tHcys and %MMA, and posi- tive correlation with %DMA, are both opposite to our previous findings in adults. We propose that upregulation of one-carbon metabolism, presumably necessary to meet the considerable demands for DNA and protein biosynthesis during periods of rapid growth, results in both increased tHcys biosynthesis and increased As methylation.

Key Words: arsenic, Bangladesh, children, cobalamin, creatinine, cysteine, dimethylarsinic acid, folate, homocysteine, monomethylarsonic acid, one-carbon metabolism. Environ Health Perspect 117:825–831 (2009). doi:10.1289/ehp.0800164 available via [Online 15 January 2009]