Mailman School of Public Health, New York, NY, USA.
Columbia University Arsenic Project Office, Mohakhali, Dhaka, Bangladesh.
Environ Res. 2021 Apr;195:110750. doi: 10.1016/j.envres.2021.110750. Epub 2021 Jan 18.
Over 57 million people in Bangladesh are chronically exposed to arsenic-contaminated drinking water. Ingested inorganic arsenic (InAs) undergoes hepatic methylation generating monomethyl- (MMAs) and dimethyl- (DMAs) arsenic species in a process that facilitates urinary As (uAs) elimination. One-carbon metabolism (OCM), a biochemical pathway that is influenced by folate and vitamin B12, facilitates the methylation of As. OCM also supports nucleotide and amino acid synthesis, particularly during periods of rapid growth such as adolescence. While folate supplementation increases As methylation and lowers blood As (bAs) in adults, little data is available for adolescents.
To examine the associations between OCM-related micronutrients and As methylation in Bangladeshi adolescents chronically exposed to As-contaminated drinking water.
We conducted a cross-sectional study of 679 Bangladeshi adolescents, including 320 boys and 359 girls aged 14-16 years. Nutritional status was assessed by red blood cell (RBC) folate, plasma folate, plasma B12 and homocysteine (Hcys). Arsenic-related outcomes included blood arsenic (bAs), urinary arsenic (uAs), and urinary arsenic metabolites expressed as a percentage of total urinary As: %InAs, %MMAs, %DMAs.
Boys had significantly lower B12, higher Hcys, higher bAs, higher uAs, higher %MMAs, and a trend toward lower RBC folate compared to girls. Therefore, regression analyses controlling for water As and BMI were sex stratified. Among girls, RBC folate was inversely associated with bAs, plasma B12 was inversely associated with uAs, and plasma Hcys was inversely associated with %MMA. Among boys, plasma folate was inversely associated with %InAs and positively associated with %DMA, RBC folate was inversely associated with %InAs and positively associated with %MMA, while Hcys was positively associated with %InAs.
These findings suggest that associations between OCM nutritional status, bAs, and distribution of As metabolites in adolescents are similar to previously reported observations in adults and in children. The As methylation findings are statistically significant among boys but not among girls; this may be related to estrogen which more strongly influences OCM in females. The inverse association between Hcys and %MMA in girls is somewhat unexpected given that Hcys is known to be an indicator of impaired OCM and low folate/B12 in adults. Overall, these results indicate that the associations between OCM-related micronutrients and arsenic methylation in adolescents are generally similar to prior findings in adults, though these associations may differ by sex. Additionally, these findings suggest that more investigation into the role of Hcys in adolescent physiology is needed, perhaps particularly for girls. Additional studies are needed to evaluate the impact of OCM and As methylation on As-related adverse health outcomes (such as cancer and cardiovascular disease) in people exposed to As during adolescence.
孟加拉国有超过 5700 万人长期饮用受砷污染的饮用水。摄入的无机砷（InAs）在肝脏中经甲基化生成单甲基砷（MMAs）和二甲基砷（DMAs），这一过程有助于砷的排泄。一碳代谢（OCM）是一种生化途径，受叶酸和维生素 B12 的影响，有助于砷的甲基化。OCM 还支持核苷酸和氨基酸的合成，特别是在青少年等快速生长时期。虽然叶酸补充剂可增加砷的甲基化并降低成人血液中的砷（bAs），但青少年的数据很少。
研究孟加拉国青少年在长期接触受砷污染的饮用水的情况下，与 OCM 相关的微量营养素与砷甲基化之间的关联。
我们对 679 名孟加拉国青少年进行了横断面研究，包括 320 名男孩和 359 名女孩，年龄在 14-16 岁之间。通过红细胞（RBC）叶酸、血浆叶酸、血浆 B12 和同型半胱氨酸（Hcys）评估营养状况。砷相关结果包括血液砷（bAs）、尿液砷（uAs）和尿液砷代谢物，以占总尿液砷的百分比表示：%InAs、%MMAs、%DMAs。
与女孩相比，男孩的 B12 水平显著较低，Hcys 水平较高，bAs、uAs、%MMAs 水平较高，RBC 叶酸水平呈趋势性降低。因此，控制水砷和 BMI 后进行了性别分层的回归分析。在女孩中，RBC 叶酸与 bAs 呈负相关，血浆 B12 与 uAs 呈负相关，血浆 Hcys 与 %MMA 呈负相关。在男孩中，血浆叶酸与 %InAs 呈负相关，与 %DMA 呈正相关，RBC 叶酸与 %InAs 呈负相关，与 %MMA 呈正相关，而 Hcys 与 %InAs 呈正相关。
这些发现表明，OCM 营养状况、bAs 和青少年砷代谢物分布之间的关联与之前在成人和儿童中报告的观察结果相似。男孩的砷甲基化发现具有统计学意义，但在女孩中没有；这可能与雌激素有关，雌激素在女性中对 OCM 的影响更强。女孩中 Hcys 与 %MMA 之间的负相关有些出乎意料，因为 Hcys 是已知的 OCM 受损和成人中叶酸/维生素 B12 水平降低的指标。总体而言，这些结果表明，青少年 OCM 相关微量营养素与砷甲基化之间的关联与成人中的关联基本相似，尽管这些关联可能因性别而异。此外，这些发现表明，需要进一步研究 Hcys 在青少年生理中的作用，尤其是对于女孩。需要进一步研究评估 OCM 和砷甲基化对处于青春期时接触砷的人群中与砷相关的不良健康结果（如癌症和心血管疾病）的影响。
