Highlight #1: Folic Acid Supplementation Lowers Blood Arsenic by Increasing as Methylation (manuscript in Preparation)

Chronic arsenic (As) exposure currently affects more than 100 million people worldwide. Methylation of ingested inorganic arsenic (InAs) to methylarsonic(MMA) and dimethylarsinic acids (DMA) relies on folate-dependent one carbon metabolism. In a recent, randomized, controlled trial, we analyzed total As and As metabolites in urine and showed that folic acid supplementation resulted in an increase in the proportion of total urinary As excreted as DMA (%uDMA) and a reduction in %uMMA and %uInAs. Since DMA has a shorter circulating half-life than other arsenic metabolites, we hypothesized that facilitation of As methylation via folic acid supplementation might lower total blood As (tbAs) concentrations. Methodological advances, using inductively coupled mass spectrometry with a dynamic reaction cell (ICP-MS-DRC) have permitted us to test this hypothesis by measuring total As and As metabolites in blood in 130 participants with low plasma folate (< 9 nmol/L) before and after 12 weeks of supplementation with folic acid (400 μg/d) or placebo. These methodological advances have also led to the discovery that blood As is a biomarker of As exposure that is directly associated with the risk for arsenic-induced skin lesions. Thus, lowering blood As with folic acid could have therapeutic potential to reduce the risk for arsenic-induced illnesses.