Influence of Cobalamin on Arsenic Metabolism in Bangladesh

BACKGROUND Arsenic is a carcinogen to which 35 million people in Bangladesh are chronically exposed. The enzymatic transfer of methyl groups to inorganic As (iAs) generates monomethylarsonic (MMA) and dimethylarsinic acids (DMA) and facilitates urinary As (uAs) elimination. This process is dependent on one-carbon metabolism, a pathway in which folate and cobalamin have essential roles in the recruitment and transfer of methyl groups. Although DMA(V) is the least toxic metabolite, increasing evidence suggests that MMA(III) may be the most cytotoxic and genotoxic As intermediary metabolite. OBJECTIVE We examined the associations between plasma cobalamin and uAs metabolites. METHODS We conducted a cross-sectional study of 778 Bangladeshi adults in which we over-sampled cobalamin-deficient participants. Participants provided blood samples for the measurement of plasma cobalamin and urine specimens for As measurements. RESULTS Cobalamin was inversely associated with the proportion of total uAs excreted as iAs (%iAs) [unstandardized regression coefficient (b) = -0.10; 95% confidence interval (CI), -0.17 to -0.02; p = 0.01] and positively associated with %MMA (b = 0.12; 95% CI, 0.05 to 0.20; p = 0.001). Both of these associations were stronger among folate-sufficient participants (%iAs: b = -0.17; 95% CI, -0.30 to -0.03; p = 0.02. %MMA: b = 0.20; 95% CI, 0.11 to 0.30; p < 0.0001), and the differences by folate status were statistically significant. CONCLUSIONS In this group of Bangladeshi adults, cobalamin appeared to facilitate the first As methylation step among folate-sufficient individuals. Given the toxicity of MMA(III), our findings suggest that in contrast to folate, cobalamin may not favorably influence As metabolism.