Nutrition, one-carbon metabolism and arsenic methylation

Exposure to arsenic (As) is a major public health concern globally. Inorganic As (InAs) undergoes hepatic methylation to form monomethyl (MMAs)- and dimethyl (DMAs)-arsenical species, facilitating urinary As elimination. MMAs^III is considerably more toxic than either InAs^III or DMAs^V, and a higher proportion of MMAs in urine has been associated with risk for a wide range of adverse health outcomes. Efficiency of As methylation differs substantially between species, between individuals, and across populations. One-carbon metabolism (OCM) is a biochemical pathway that provides methyl groups for the methylation of As, and is influenced by folate and other micronutrients, such as vitamin B₁₂, choline, betaine and creatine. A growing body of evidence has demonstrated that OCM-related micronutrients play a critical role in As methylation. This review will summarize observational epidemiological studies, interventions, and relevant experimental evidence examining the role that OCM-related micronutrients have on As methylation, toxicity of As, and risk for associated adverse health-related outcomes. There is fairly robust evidence supporting the impact of folate on As methylation, and some evidence from case-control studies indicating that folate nutritional status influences risk for As-induced skin lesions and bladder cancer. However, the potential for folate to be protective for other As-related health outcomes, and the potential beneficial effects of other OCM-related micronutrients on As methylation and risk for health outcomes are less well studied and warrant additional research.