Serum folate levels and urinary arsenic methylation profiles in the US population: NHANES, 2003–2012

Arsenic is a prevalent environmental contaminant, and its folate-dependent methylation is important for detoxification in the body. In this study, we investigated the association between serum folate levels and methylation using data from the US National Health and Nutrition Examination Survey (NHANES) (2003–2012) (N = 11,016). Multivariate linear regression and penalized spline regression models were used to examine the association and possible upper limit of folate level regarding its impact on methylation in children (≤18 years) and adults (>18 years), respectively. Serum folate levels, methylation metabolites including urinary monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)), and demographic variables were extracted from NHANES. Results showed that urinary percentage of DMA(V) (%DMA(V)) was positively associated with log(serum folate levels) after adjustment in children (β = 1.93, p < 0.01); urinary percentage of MMA(V) (%MMA(V)) was positively associated with log (serum folate levels) after adjustment in adults (β = 0.40, p < 0.01). No upper limit of folate level regarding its impact on arsenic methylation was identified. More than 50% of Non-Hispanic black and smokers with high total urinary arsenic levels had low serum folate levels. Our results indicate that folate promotes arsenic methylation, but the patterns are different in children versus in adults. Future interventions may be needed for the population exposed to high level of arsenic but with low serum folate to protect against the potential adverse health effects of arsenic.