Nutrients in one-carbon metabolism and urinary arsenic methylation in the National Health and Nutrition Examination Survey (NHANES) 2003-2004

- Majority of toxic arsenic exposure in the U.S. is from food.
- One-carbon nutrients are independently associated with urinary As metabolism.
- High metabolic levels of folate and dietary Vit B6 may mitigate inAs toxicity.
- High plasma tHcys and dietary Vit B12 may increase susceptibility to inAs exposure.
- NHANES results corroborate those seen in highly exposed, malnourished populations.

Exposure to inorganic arsenic (inAs), a potent toxicant, occurs primarily through ingestion of food and water. The efficiency with which it is methylated to mono and dimethyl arsenicals (MMA and DMA) affects toxicity. Folate, vitamins B12 and B6 are required for 1C metabolism, and studies have found that higher levels of these nutrients increase methylation capacity and are associated with protection against adverse health effects from inAs, especially in undernourished populations. Our aim was to determine whether 1C-related nutrients are associated with greater inAs methylation capacity in a general population sample with overall adequate nutrition and low levels of As exposure. Univariate and multivariable regression models were used to evaluate the relationship of dietary and blood nutrients to urinary As methylation in the National Health and Nutrition Examination Survey (NHANES) 2003-2004. Outcome variables were the percent of the sum of inAs and methylated As species (inAs + MMA + DMA) excreted as inAs, MMA, and DMA, and the ratio of MMA:DMA. In univariate models, dietary folate, vitamin B6 and protein intake were associated with lower urinary inAs% and greater DMA% in adults (≥ 18 years), with similar trends in children (6-18). In adjusted models, vitamin B6 intake (p = 0.011) and RBC folate (p = 0.036) were associated with lower inAs%, while dietary vitamin B12 was associated with higher inAs% (p = 0.002) and lower DMA% (p = 0.030). Total plasma homocysteine was associated with higher MMA% (p = 0.004) and lower DMA% (p = 0.003), but not with inAs%; other blood nutrients showed no association with urinary As. Although effect size is small, these findings suggest that 1C nutrients can influence inAs methylation and potentially play an indirect role in reducing toxicity in a general population sample.

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