Arsenic Health Effects Research Group, School of Public Health, University of California, Berkeley, California 94720, USA.
Environ Health Perspect. 2011 Sep;119(9):1308-13. doi: 10.1289/ehp.1003393. Epub 2011 Jun 7.
Ingested inorganic arsenic (InAs) is methylated to monomethylated (MMA) and dimethylated metabolites (DMA). Methylation may have an important role in arsenic toxicity, because the monomethylated trivalent metabolite [MMA(III)] is highly toxic.
We assessed the relationship of creatinine and nutrition--using dietary intake and blood concentrations of micronutrients--with arsenic metabolism, as reflected in the proportions of InAS, MMA, and DMA in urine, in the first study that incorporated both dietary and micronutrient data.
We studied methylation patterns and nutritional factors in 405 persons who were selected from a cross-sectional survey of 7,638 people in an arsenic-exposed population in West Bengal, India. We assessed associations of urine creatinine and nutritional factors (19 dietary intake variables and 16 blood micronutrients) with arsenic metabolites in urine.
Urinary creatinine had the strongest relationship with overall arsenic methylation to DMA. Those with the highest urinary creatinine concentrations had 7.2% more arsenic as DMA compared with those with low creatinine (p < 0.001). Animal fat intake had the strongest relationship with MMA% (highest tertile animal fat intake had 2.3% more arsenic as MMA, p < 0.001). Low serum selenium and low folate were also associated with increased MMA%.
Urine creatinine concentration was the strongest biological marker of arsenic methylation efficiency, and therefore should not be used to adjust for urine concentration in arsenic studies. The new finding that animal fat intake has a positive relationship with MMA% warrants further assessment in other studies. Increased MMA% was also associated, to a lesser extent, with low serum selenium and folate.
摄入的无机砷（InAs）被甲基化为一甲基（MMA）和二甲基代谢物（DMA）。甲基化在砷毒性中可能具有重要作用，因为三价一甲基代谢物 [MMA(III)] 具有很高的毒性。
我们评估了肌酐和营养状况——使用饮食摄入和血液中微量元素浓度——与砷代谢的关系，这反映在尿液中 InAs、MMA 和 DMA 的比例上，这是第一项综合考虑饮食和微量元素数据的研究。
我们研究了来自印度西孟加拉邦一个砷暴露人群的 7638 人横断面调查中选出的 405 人的甲基化模式和营养因素。我们评估了尿液肌酐和营养因素（19 个饮食摄入变量和 16 个血液微量元素）与尿液中砷代谢物的关联。
尿肌酐与 DMA 对砷的总体甲基化关系最强。与肌酐低的人相比，肌酐浓度最高的人有 7.2%的砷以 DMA 形式存在（p < 0.001）。动物脂肪摄入量与 MMA%的关系最强（最高 tertile 的动物脂肪摄入量有 2.3%的砷以 MMA 形式存在，p < 0.001）。低血清硒和低叶酸也与 MMA%增加有关。
尿肌酐浓度是砷甲基化效率最强的生物标志物，因此在砷研究中不应将其用于调整尿液浓度。动物脂肪摄入量与 MMA%呈正相关的新发现值得在其他研究中进一步评估。MMA%增加也与血清硒和叶酸水平较低有一定的相关性。
