Folate, homocysteine, and arsenic metabolism in arsenic-exposed individuals in Bangladesh

Chronic exposure to arsenic is occurring throughout South and East Asia due to groundwater contamination of well water. Variability in susceptibility to arsenic toxicity may be related to nutritional status. Arsenic is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) via one-carbon metabolism, a biochemical pathway that is dependent on folate. The majority of one-carbon metabolism methylation reactions are devoted to biosynthesis of creatine, the precursor of creatinine. Our objectives of this cross-sectional study were to characterize the relationships among folate, cobalamin, homocysteine, and arsenic metabolism in Bangladeshi adults. Water arsenic, urinary arsenic, urinary creatinine, plasma folate, cobalamin, and homocysteine were assessed in 1,650 adults; urinary arsenic metabolites were analyzed for a subset of 300 individuals. The percentage of DMA in urine was positively associated with plasma folate (r = 0.14, p = 0.02) and negatively associated with total homocysteine (tHcys; r = -0.14, p = 0.01). Conversely, percent MMA was negatively associated with folate (r = -0.12, p = 0.04) and positively associated with tHcys (r = 0.21, p = 0.0002); percent inorganic arsenic (InAs) was negatively associated with folate (r = -0.12, p = 0.03). Urinary creatinine was positively correlated with percent DMA (r = 0.40 for males, p < 0.0001; 0.25 for females, p = 0.001), and with percent InAs (r = -0.45 for males, p < 0.0001; -0.20 for females, p = 0.01). Collectively, these data suggest that folate, tHcys, and other factors involved in one-carbon metabolism influence arsenic methylation. This may be particularly relevant in Bangladesh, where the prevalence of hyperhomocysteinemia is extremely high.     

Polymorphisms in 1-carbon metabolism, epigenetics and folate-related pathologies

Folate-mediated 1-carbon metabolism is a network of interconnected metabolic pathways necessary for the synthesis of purine nucleotides, thymidylate and the remethylation of homocysteine to methionine. Disruptions in this pathway influence both DNA synthesis and stability and chromatin methylation, and result from nutritional deficiencies and common gene variants. The mechanisms underlying folate-associated pathologies and developmental anomalies have yet to be established. This review focuses on the relationships among folate-mediated 1-carbon metabolism, chromatin methylation and human disease, and the role of gene-nutrient interactions in modifying epigenetic processes.     

Folate and arsenic metabolism: a double-blind, placebo-controlled folic acid-supplementation trial in Bangladesh

BACKGROUND: Populations in South and East Asia and many other regions of the world are chronically exposed to arsenic-contaminated drinking water. To various degrees, ingested inorganic arsenic (InAs) is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) via folate-dependent one-carbon metabolism; impaired methylation is associated with adverse health outcomes. Consequently, folate nutritional status may influence arsenic methylation and toxicity. OBJECTIVE: The objective of this study was to test the hypothesis that folic acid supplementation of arsenic-exposed adults would increase arsenic methylation. DESIGN: Two hundred adults in a rural region of Bangladesh, previously found to have low plasma concentrations of folate (相似文献   

Gender and age differences in the metabolism of inorganic arsenic in a highly exposed population in Bangladesh

Although genetic polymorphisms have been shown to explain some of the large variation observed in the metabolism of inorganic arsenic there may be several other factors playing an important role, e.g. nutrition. The objective of this study was to elucidate the influence of various factors on current arsenic exposure and metabolism in Matlab, a rural area in Bangladesh, where elevated water arsenic concentrations and malnutrition are prevalent. In total 1571 individuals, randomly selected from all inhabitants above 5 years of age, were investigated by measuring arsenic in urine and drinking water. In a subset of 526 randomly selected individuals, arsenic metabolites were speciated using HPLC coupled to inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). A significant association was observed between arsenic in urine and drinking water (R2=0.41). The contribution to urinary arsenic from arsenic exposure from food and other water sources was calculated to be almost 50microg/L. The individuals in the present study had remarkably efficient methylation, in spite of high exposure and prevalence of malnutrition. Gender and age were major factors influencing arsenic metabolism in this population with a median of 77microg/L of arsenic in urine (range: 0.5-1994microg/L). Women had higher arsenic methylation efficiency than men, but only in childbearing age, supporting an influence of sex hormones. Overall, exposure level of arsenic, gender and age explained at most 30% of the variation in the present study, indicating that genetic polymorphisms are the most important factor influencing the metabolism of inorganic arsenic.     

血清叶酸相关代谢与出生缺陷发生的关系研究

目的 比较出生缺陷高发和低发地区--山西吕梁和北京怀柔地区孕妇血清叶酸、维生素B12及其代谢产物同型半胱氨酸水平,探讨造成两地出生缺陷发生率差异的营养学因素.方法 选择吕梁地区的140名孕妇和怀柔地区的133名孕妇作为研究对象,采集研究对象的静脉血,比较两地区孕妇血清叶酸、维生素B12和同型半胱氨酸水平差异.结果 吕梁地区孕妇血清平均叶酸、维生素B12水平显著低于怀柔地区(t值分别为6.10、13.77,均P<0.05).同时吕梁地区孕妇血清同型半胱氨酸水平显著高于怀柔地区(t=15.32,P<0.05),吕梁地区叶酸、维生素B12缺乏率显著高于怀柔地区(χ2值分别为7.84、61.02,均P<0.05).结论 出生缺陷高发地区孕妇血清叶酸、维生素B12水平显著偏低,叶酸相关一碳单位代谢水平异常在一定程度上解释了高出生缺陷发生率的原因.     

Social implications of arsenic poisoning in Bangladesh

Besides its toxicity, groundwater arsenic contamination creates widespread social problems for its victims and their families in Bangladesh. There is, for instance, a tendency to ostracise arsenic-affected people, arsenicosis being thought of as a contagious disease. Within the community, arsenic-affected people are barred from social activities and often face rejection, even by their immediate family members. Women with visible arsenicosis symptoms are unable to get married and some affected housewives are divorced by their husbands. Children with symptoms are not sent to school in an effort to hide the problem. This paper employs mainly qualitative methods to interpret people's understandings about the toxic impact of groundwater arsenic poisoning on their social lives. Arsenic-affected patients in southwest Bangladesh were asked to determine their 'own priorities' in measuring arsenic toxicity on their social activities and to explore their perceptions about their own survival strategies. We found that patients' experiences reveal severe negative social impacts, and a sharp difference of perceptions about arsenic and social issues between arsenicosis patients and unaffected people.     

Risk assessment of arsenic mitigation options in Bangladesh

The provision of alternative water sources is the principal arsenic mitigation strategy in Bangladesh, but can lead to risk substitution. A study of arsenic mitigation options was undertaken to assess water quality and sanitary condition and to estimate the burden of disease associated with each technology in disability-adjusted life years (DALYs). Dugwells and pond-sand filters showed heavy microbial contamination in both dry and monsoon seasons, and the estimated burden of disease was high. Rainwater was of good quality in the monsoon but deteriorated in the dry season. Deep tubewells showed microbial contamination in the monsoon but not in the dry season and was the only technology to approach the World Health Organization's reference level of risk of 10-6 DALYs. A few dugwells and one pond-sand filter showed arsenic in excess of 50 microg/L. The findings suggest that deep tubewells and rainwater harvesting provide safer water than dugwells and pond-sand filters and should be the preferred options.     

Respiratory effects and arsenic contaminated well water in Bangladesh

Arsenic in drinking water causes a widespread concern in Bangladesh, where a major proportion of tube wells is contaminated. Arsenic ingestion causes skin lesions, which is considered as definite exposure. A prevalence comparison study of respiratory effects among subjects with and without arsenic exposure through drinking water was conducted in Bangladesh. Exposed participants were recruited through health awareness campaign programs. Unexposed participants were randomly selected, where tubewells were not contaminated with arsenic. A total of 169 individuals participated (44 exposed individuals exhibiting skin lesions; 125 unexposed individuals). The arsenic concentrations ranged from 136 to 1000 micro g l(-1). The information regarding respiratory system signs and symptoms were also collected and the analyses were confined to nonsmokers. The crude prevalence ratio for chronic bronchitis and chronic cough amounted to 2.1 (95% CI 0.7-6.1). The prevalence ratios for chronic bronchitis increased with increasing exposure, i.e., 1.0, 1.6, 2.7 and 2.6 using unexposed as the reference. The prevalence ratios for chronic cough were 1.0, 1.6, 2.7 and 2.6 for the exposure categories, using the same unexposed as the reference. The dose-response trend was the same (P < 0.1) for both conditions. These results add to evidence that long-term ingestion of arsenic exposure can cause respiratory effects.     

膳食营养素对砷毒性的影响

环境砷暴露是一个世界范围内的公共卫生问题,长期接触无机砷与心血管疾病、糖尿病以及恶性肿瘤等疾病关系密切。膳食结构的不同以及某些特定营养素的摄入对砷的致病效应可能产生重要影响。本文概述了膳食营养素对砷毒性的影响,为后续砷毒性研究以及通过营养干预来降低与砷有关的疾病风险提供参考。     

Groundwater arsenic contamination in Bangladesh and West Bengal, India

Nine districts in West Bengal, India, and 42 districts in Bangladesh have arsenic levels in groundwater above the World Health Organization maximum permissible limit of 50 microg/L. The area and population of the 42 districts in Bangladesh and the 9 districts in West Bengal are 92,106 km(2) and 79.9 million and 38,865 km(2) and 42.7 million, respectively. In our preliminary study, we have identified 985 arsenic-affected villages in 69 police stations/blocks of nine arsenic-affected districts in West Bengal. In Bangladesh, we have identified 492 affected villages in 141 police stations/blocks of 42 affected districts. To date, we have collected 10,991 water samples from 42 arsenic-affected districts in Bangladesh for analysis, 58,166 water samples from nine arsenic-affected districts in West Bengal. Of the water samples that we analyzed, 59 and 34%, respectively, contained arsenic levels above 50 microg/L. Thousands of hair, nail, and urine samples from people living in arsenic-affected villages have been analyzed to date; Bangladesh and West Bengal, 93 and 77% samples, on an average, contained arsenic above the normal/toxic level. We surveyed 27 of 42 districts in Bangladesh for arsenic patients; we identified patients with arsenical skin lesions in 25 districts. In West Bengal, we identified patients with lesions in seven of nine districts. We examined people from the affected villages at random for arsenical dermatologic features (11,180 and 29,035 from Bangladesh and West Bengal, respectively); 24.47 and 15.02% of those examined, respectively, had skin lesions. After 10 years of study in West Bengal and 5 in Bangladesh, we feel that we have seen only the tip of iceberg.     

Cancer burden from arsenic in drinking water in Bangladesh

We assessed the potential burden of internal cancers due to arsenic exposure in Bangladesh. We estimated excess lifetime risks of death from liver, bladder, and lung cancers using an exposure distribution, death probabilities, and cancer mortality rates from Bangladesh and dose-specific relative risk estimates from Taiwan. Results indicated at least a doubling of lifetime mortality risk from liver, bladder, and lung cancers (229.6 vs 103.5 per 100 000 population) in Bangladesh owing to arsenic in drinking water.     

Rural communities' preferences for arsenic mitigation options in Bangladesh

In the context of arsenic contamination of groundwater in Bangladesh, this paper analyses rural people's preferences for arsenic-free drinking water options. A particular focus is on rural households' willingness to pay for piped water supply which can provide a sustainable solution to the arsenic problem, and how the preference for piped water supply compares with that for various other household/community-based arsenic mitigation technologies. The analysis is based on data collected in a survey of over 2700 households in rural Bangladesh. Six arsenic mitigation technologies were selected for the study: three-kolshi (pitcher) method, activated alumina method (household-based and community-based), dugwell, pond sand filter and deep tubewell (handpump). The survey results indicate that, after taking into consideration the initial and recurring costs, convenience, associated risks and the advantages and disadvantages of each selected technology, the preference of the rural people is overwhelmingly in favor of deep tubewells, followed by the three-kolshi method. The analysis reveals a strong demand for piped water in both arsenic-affected and arsenic-free rural areas, and scope of adequate cost recovery. Between piped water and other arsenic mitigation technologies, the preference of the rural people is found to be predominantly in favor of the former.     

Community wells to mitigate the arsenic crisis in Bangladesh

OBJECTIVE: To monitor the effectiveness of deep community wells in reducing exposure to elevated levels of arsenic in groundwater pumped from shallower aquifers. METHODS: Six community wells ranging in depth from 60 m to 140 m were installed in villages where very few of the wells already present produced safe water. By means of flow meters and interviews with villagers carrying water from the community wells, a study was made of the extent to which these were used during one year. The results were compared with household and well data obtained during a previous survey in the same area. FINDINGS: The mean arsenic concentration in water pumped from wells already in use in the villages where the community wells, were installed was 180 +/- 140 micrograms/l (n = 956). Monthly sampling for 4-11 months showed that arsenic levels in groundwater from five of the six newly installed wells were consistently within the WHO guideline value of 10 micrograms/l for drinking-water. One of these wells met the Bangladesh standard of 50 micrograms/l arsenic but failed to meet the WHO guideline values for manganese and uranium in drinking-water. The community wells were very popular. Many women walked hundreds of metres each day to fetch water from them. On average, 2200 litres were hand-pumped daily from each community well, regardless of the season. CONCLUSION: A single community well can meet the needs of some 500 people residing within a radius of 150 m of it in a densely populated village. Properly monitored community wells should become more prominent in campaigns to reduce arsenic exposure in Bangladesh. Between 8000 and 10,000 deep community wells are needed to provide safe water for the four to five million people living in the most severely affected parts of the country.     

Reduction in urinary arsenic levels in response to arsenic mitigation efforts in Araihazar, Bangladesh

BACKGROUND: There is a need to identify and evaluate an effective mitigation program for arsenic exposure from drinking water in Bangladesh. OBJECTIVE: We evaluated the effectiveness of a multifaceted mitigation program to reduce As exposure among 11,746 individuals in a prospective cohort study initiated in 2000 in Araihazar, Bangladesh, by interviewing participants and measuring changes in urinary As levels. METHODS: The interventions included a) person-to-person reporting of well test results and health education; b) well labeling and village-level health education; and c) installations of 50 deep, low-As community wells in villages with the highest As exposure. RESULTS: Two years after these interventions, 58% of the 6,512 participants with unsafe wells (As >/=50 microg) at baseline had responded by switching to other wells. Well labeling and village-level health education was positively related to switching to safe wells (As < 50 mug/L) among participants with unsafe wells [rate ratio (RR) = 1.84; 95% confidence interval (CI), 1.60-2.11] and inversely related to any well switching among those with safe wells (RR = 0.80; 95% CI, 0.66-0.98). The urinary As level in participants who switched to a well identified as safe (< 50 microg As/L) dropped from an average of 375 microg As/g creatinine to 200 microg As/g creatinine, a 46% reduction toward the average urinary As content of 136 microg As/g creatinine for participants that used safe wells throughout. Urinary As reduction was positively related to educational attainment, body mass index, never-smoking, absence of skin lesions, and time since switching (p for trend < 0.05). CONCLUSIONS: Our study shows that testing of wells and informing households of the consequences of As exposure, combined with installation of deep community wells where most needed, can effectively address the continuing public health emergency from arsenic in drinking water in Bangladesh.     

Spatial modeling of households' knowledge about arsenic pollution in Bangladesh

Arsenic in drinking water is an important public health issue in Bangladesh, which is affected by households' knowledge about arsenic threats from their drinking water. In this study, spatial statistical models were used to investigate the determinants and spatial dependence of households' knowledge about arsenic risk. The binary join matrix/binary contiguity matrix and inverse distance spatial weight matrix techniques are used to capture spatial dependence in the data. This analysis extends the spatial model by allowing spatial dependence to vary across divisions and regions. A positive spatial correlation was found in households' knowledge across neighboring districts at district, divisional and regional levels, but the strength of this spatial correlation varies considerably by spatial weight. Literacy rate, daily wage rate of agricultural labor, arsenic status, and percentage of red mark tube well usage in districts were found to contribute positively and significantly to households' knowledge. These findings have policy implications both at regional and national levels in mitigating the present arsenic crisis and to ensure arsenic-free water in Bangladesh.     

Water arsenic exposure and children's intellectual function in Araihazar, Bangladesh

Exposure to arsenic has long been known to have neurologic consequences in adults, but to date there are no well-controlled studies in children. We report results of a cross-sectional investigation of intellectual function in 201 children 10 years of age whose parents participate in our ongoing prospective cohort study examining health effects of As exposure in 12,000 residents of Araihazar, Bangladesh. Water As and manganese concentrations of tube wells at each child's home were obtained by surveying all wells in the study region. Children and mothers came to our field clinic, where children received a medical examination in which weight, height, and head circumference were measured. Children's intellectual function on tests drawn from the Wechsler Intelligence Scale for Children, version III, was assessed by summing weighted items across domains to create Verbal, Performance, and Full-Scale raw scores. Children provided urine specimens for measuring urinary As and creatinine and were asked to provide blood samples for measuring blood lead and hemoglobin concentrations. Exposure to As from drinking water was associated with reduced intellectual function after adjustment for sociodemographic covariates and water Mn. Water As was associated with reduced intellectual function, in a dose-response manner, such that children with water As levels > 50 microg/L achieved significantly lower Performance and Full-Scale scores than did children with water As levels < 5.5 microg/L. The association was generally stronger for well-water As than for urinary As.     

Variability in human metabolism of arsenic

Estimating the nature and extent of human cancer risks due to arsenic (As) in drinking water is currently of great concern, since millions of persons worldwide are exposed to arsenic, primarily through natural enrichment of drinking water drawn from deep wells. Humans metabolize and eliminate As through oxidative methylation and subsequent urinary excretion. While there is debate as to the role of methylation in activation/detoxification, variations in arsenic metabolism may affect individual risks of toxicity and carcinogenesis. Using data from three populations, from Mexico, China, and Chile, we have analyzed the distribution in urine of total arsenic and arsenic species (inorganic arsenic (InAs), monomethyl arsenic (MMA), and dimethyl arsenic (DMA). Data were analyzed in terms of the concentration of each species and by evaluating MMA:DMA and (MMA+DMA):InAs ratios. In all persons most urinary As was present as DMA. Male:female differences were discernible in both high- and low-exposure groups from all three populations, but the gender differences varied by populations. The data also indicated bimodal distributions in the ratios of DMA to InAs and to MMA. While the gene or genes responsible for arsenic methylation are still unknown, the results of our studies among the ethnic groups in this study are consistent with the presence of functional genetic polymorphisms in arsenic methylation leading to measurable differences in toxicity. This analysis highlights the need for continuing research on the health effects of As in humans using molecular epidemiologic methods.