Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, NY, USA.
Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh.
Environ Int. 2024 May;187:108715. doi: 10.1016/j.envint.2024.108715. Epub 2024 May 3.
Inorganic arsenic is metabolized to monomethyl- (MMAs) and dimethyl- (DMAs) species via one-carbon metabolism (OCM); this facilitates urinary arsenic elimination. OCM is influenced by folate and vitamin B12 and previous randomized control trials (RCTs) showed that folic acid (FA) supplementation increases arsenic methylation in adults. This RCT investigated the effects of FA + B12 supplementation on arsenic methylation in children, a key developmental stage where OCM supports growth.
A total of 240 participants (8-11 years, 53 % female) drinking from wells with arsenic concentrations > 50 μg/L, were encouraged to switch to low arsenic wells and were randomized to receive 400 μg FA + 5 μg B12 or placebo daily for 12-weeks. Urine and blood samples were collected at baseline, week 1 (only urine) and week 12. Generalized estimated equation (GEE) models were used to assess treatment effects on arsenic species in blood and urine.
At baseline, the mean ± SD total blood and urinary arsenic were 5.3 ± 2.9 μg/L and 91.2 ± 89.5 μg/L. Overall, total blood and urine arsenic decreased by 11.7% and 17.6%, respectively, at the end of follow up. Compared to placebo, the supplementation group experienced a significant increase in the concentration of blood DMAs by 14.0% (95% CI 5.0, 25.0) and blood secondary methylation index (DMAs/MMAs) by 0.19 (95% CI: 0.09, 0.35) at 12 weeks. Similarly, there was a 1.62% (95% CI: 0.43, 20.83) significantly higher urinary %DMAs and -1.10% (95% CI: -1.73, -0.48) significantly lower urinary %MMAs in the supplementatio group compared to the placebo group after 1 week. The direction of the changes in the urinary %iAs, %MMAs, and %DMAs at week 12 were consistent with those at week 1, though estimates were not significant. Treatment effects were stronger among participants with higher baseline blood arsenic concentrations. Results were consistent across males and females, and participants with higher and lower folate and B12 status at baseline.
This RCT confirms that FA + B12 supplementation increases arsenic methylation in children as reflected by decreased MMAs and increased DMAs in blood and urine. Nutritional interventions may improve arsenic methylation and elimination in children, potentially reducing arsenic toxicity while also improving nutritional status.
无机砷通过一碳代谢（OCM）转化为单甲基（MMAs）和二甲基（DMAs）；这有助于砷的尿液排泄。OCM 受叶酸和维生素 B12 的影响，之前的随机对照试验（RCT）表明，叶酸（FA）补充剂可增加成年人的砷甲基化。本 RCT 研究了 FA+B12 补充剂对儿童砷甲基化的影响，OCM 支持儿童生长，儿童是这一关键发育阶段。
共有 240 名参与者（8-11 岁，53%为女性）从砷浓度>50μg/L 的水井中饮水，他们被鼓励切换到低砷水井，并随机接受每天 400μg FA+5μg B12 或安慰剂治疗 12 周。在基线、第 1 周（仅尿液）和第 12 周采集尿液和血液样本。使用广义估计方程（GEE）模型评估治疗对血液和尿液中砷形态的影响。
在基线时，平均±SD 全血和尿砷分别为 5.3±2.9μg/L 和 91.2±89.5μg/L。总的来说，在随访结束时，全血和尿液中的砷分别下降了 11.7%和 17.6%。与安慰剂相比，补充组血液中 DMAs 的浓度增加了 14.0%（95%CI：5.0，25.0），血液中二级甲基化指数（DMAs/MMAs）增加了 0.19（95%CI：0.09，0.35），12 周时，补充组尿液中的%DMAs 增加了 1.62%（95%CI：0.43，20.83），尿液中的%MMAs 减少了-1.10%（95%CI：-1.73，-0.48）。与安慰剂组相比，1 周时补充组尿液中的%iAs、%MMAs 和%DMAs 变化方向一致，但估计值无统计学意义。在基线时血液砷浓度较高的参与者中，治疗效果更强。12 周时的结果在血液和尿液中的 MMAs 和 DMAs 方面与 1 周时的结果一致，尽管估计值没有统计学意义。在男性和女性以及基线叶酸和 B12 水平较高和较低的参与者中，结果一致。
本 RCT 证实，FA+B12 补充剂可增加儿童砷的甲基化，表现在血液和尿液中 MMAs 减少和 DMAs 增加。营养干预可能改善儿童的砷甲基化和排泄，潜在地降低砷毒性，同时改善营养状况。
