Arsenic contamination of drinking water is a public health problem in Bangladesh [1]. Extent of the drinking water arsenic contamination is unprecedented in rural areas of the country. Approximately one-third of the hand tube wells in Bangladesh contain arsenic more than 10 μg/L, the recommended level of arsenic in drinking water by the WHO [2]. Chronic exposure to arsenic has the potentials to cause wide ranges of carcinogenic and non-carcinogenic health effects such as cancer of the skin and internal organs, diabetes mellitus, hypertension, and respiratory conditions [3–10]. Among the non-carcinogenic effects, chronic arsenic exposure has also been reported to increase the risk of foetal and infant deaths [11–16].

Drinking water in Bangladesh contains mostly inorganic arsenic. Inorganic arsenic, once ingested is excreted through urine in human [17]. A series of reduction and oxidation methylation reactions occur in liver to form monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) [18]. Endogenous thiols probably play a critical role in the metabolic conversion of As (III) and As (V) species. Glutathion is likely to act as a reducing agent for converting As (V) species into As (III), which can then accept a methyl group from S-Adenosylmethionine (SAM) to produce the methyl arsenic (V) species [19]. Diet containing methionine, choline, folate, and other nutrients may be the source of this methyl group from SAM. However, the role of nutritional factors on arsenic metabolism and toxicity is yet to be fully explored.

Limited studies have indicated that poor nutritional status may increase the risk of arsenic related health effects [20–24]. Participants with poor nutritional status (weight below 80% of the standard body weight for their age and sex) were reported from West Bengal, India to have an overall 1.6 fold-increase (for males = 1.5, females = 2.1) in the prevalence of keratoses, suggesting that malnutrition may increase the susceptibility for arsenic toxicity [22]. Arsenic affected people of south western Taiwan and the Antofagasta region in northern Chile were reported to have a low socio-economic status and poor nutritional status [20,21,23,24]. Experimental studies have shown that rabbits fed diets containing low methionine, choline, or proteins have a decrease in arsenic methylation and an increase in tissue retention of arsenic, especially in the liver [25]. Decrease in urinary excretion of dimethyl arsinic acid (DMA) was also observed in another study where mice were fed a choline-deficient diet [26]. Lower Body mass index (BMI) was reported among the arsenicosis patients compared to the unexposed population in a previous study in Bangladesh [27]. In a recent study in Bangladesh, Heck et al observed that higher intakes of protein, methionine, and cysteine were associetd with 10–15% greater total urinary arsenic excretion, after adjusting for total energy intake, body weight, sex, age, tobacco use, and intake of some other nutrients [28]. However, a study from Atacameño in northern Chile reported no evidence of malnutrition among individuals with arsenic induced skin lesions [29]. Each of the families with arsenic-induced skin lesions consumed many vegetables, including carrots, everyday. This might be due to that high carotene intake and vitamin A do not prevent arsenic-induced skin lesions.

Malnutrition is highly prevalent in rural Bangladesh [27]. Malnourished women are likely to have higher risk of adverse pregnancy outcomes. Malnutrition during pregnancy may increase the risk of intra-uterine growth, low birth weight baby, stunting, severe wasting and foetal death [30,31]. Experimental studies on ewes and rats have shown that malnutrition during pregnancy resulted in modifications of embryo development leading to abnormalities of the offspring in late gestation and postnatal periods [32–34]. Chronic exposure to arsenic through drinking water also increases the risk of adverse pregnancy outcomes [11–16]. The combined effects of malnutrition and chronic arsenic exposure may worsen the adverse pregnancy outcomes. Therefore, the purpose of this case-control study was to determine the association between chronic arsenic exposure and nutritional status of the women of child bearing age in rural Bangladesh.

Table 1 presents the baseline characteristics, arsenic exposure and nutritional status of the cases and controls. Cases are similar to the controls with respect to its baseline characteristics except total monthly household income, arsenic concentrations and body weight.

The combined effects of arsenic concentration and duration of arsenic exposure on nutritional status are presented in Table 3. For arsenic concentration of 100 μg/L with an exposure of ≤10 years, the risk estimate for malnutrition is high. The reference group is those who had concentrations not exceeding 50 μg/L regardless of the duration of exposure.

In this study, we assessed the risk of malnutrition among the women of reproductive age i.e., 20–45 years at several concentrations of arsenic in drinking water in rural Bangladesh. The findings suggest an association between chronic arsenic exposure through drinking water and malnutrition. An overall 1.9 fold (95% CI = 1.1–3.6) increase in poor nutritional status was observed among the arsenic exposed women compared to women who were not exposed to arsenic more than 50 μg/L.

Risks were generally higher for those exposed to arsenic more than 100 μg/L. Excess risk was observed among the women who were exposed to arsenic more than 100 μg/L and for ≤10 years. Women exposed to arsenic more than 50 μg/L for more than 10 years showed weaker association. This may be due to inaccurate self reporting of arsenic exposure duration by the participants.

Similar observations have been reported from West Bengal, India and Taiwan. In an arsenic-exposed population in West Bengal body weight was negatively associated with the occurrence of keratosis [22] and in Taiwan vascular effects (blackfoot-disease) were associated with undernourishment (high intake of sweet potatoes, low intake of rice and vegetables) [39]. In Taiwan, a low serum β-carotene concentration was associated with a higher prevalence of arsenic-related skin-cancer [40] and ischemic heart disease [41].

It is not clear how the nutritional status of an individual influences the arsenic metabolism and toxicity process. Experimental studies in rabbits have shown that diets with low amount of methionine, choline or proteins reduced the urinary excretion of DMA, an end product of methylation [25]. Whether it is also applicable for humans is not known. Zinc has been suggested to influence arsenic toxicity [5] and mice fed a selenium-deficient diet showed a slower elimination of arsenic than selenium-sufficient mice [42]. Also, dietary selenium supplementation was found to prevent cytotoxic effects of arsenic mice in vivo [43]. Given that a deficiency in folate and vitamin B12 might lead to decreased levels of S-adenosylmethyltransferase [44], it may also result in decreased methylation of arsenic. Indeed, folic acid was found to protect mouse embryo fibroblasts against cytotoxicity of arsenic [45].

Chronic arsenic exposure has been reported to be associated with human adverse pregnancy outcomes in a few studies [11–14,16]. Animal model experimentation have also shown the toxicity of several forms of arsenic on pregnancy outcomes including malformations [46]. Recent studies reported that arsenic crosses the human placenta [47], although more than 90 percent of the arsenic in plasma and urine was in the form of dimethylarsenic acid indicating an increase in the methylation of arsenic during pregnancy. Maternal toxicity has also found to be associated with the adverse developmental effects of arsenic exposure. There are instances that the maternal toxicity is the causative factor in abnormal development of the embryos [48]. This is probably due to induction of metallothionein in the maternal liver that leads to a systemic redistribution of zinc and a transitory, but developmentally adverse zinc deficiency. These effects were produced in pregnant rat by arsenate. Exposure to arsenic also exerted direct adverse effects on explanted rodent embryos exposed to arsenic in the absence of the maternal system. However, a poor correlation was found on maternal and developmental toxicity relationship in an extensive literature analysis [49]. Therefore, arsenic is likely to have direct toxic effects on embryos in vivo, but its effects might be exacerbated by external toxicity [4]. Therefore, combined effects of malnutrition and chronic arsenic exposure may worsen the reproductive health of the women of particular age group.

To the best of our knowledge, this is the first study carried out to determine the effect of chronic arsenic exposure on the nutritional status of the women of reproductive age. None of the study participants had visible arsenical skin lesions. Therefore, the observed risk of malnutrition in this study is likely to be the effect of chronic arsenic exposure than to be the consequence of arsenical skin lesions.

We used BMI as the indicator of nutritional status in this study. Of the anthropometric indices, body mass index is considered to be more nutritionally than genetically related [50]. Thus it is appropriate to use BMI as an indicator of the adult nutritional status. However, body mass index is not the only indicator for measuring nutritional status. So, further studies including detail assessment of nutritional status together with evaluation of dietary intake and blood studies is required to understand the dynamics of malnutrition.

In case-control studies, exposure measurement remains as an important issue. In our study, we only collected water sample from one tube well for each participant’s exposure measurement. This single water measurement may not represent the historical arsenic exposure over time. However, due to absence of any reliable information on past exposure, it was essential to assume that arsenic concentrations from the tube wells had been relatively constant over time. The historical consistency of arsenic concentration is of particular concern with shallow ground water, which might be subject to greater fluctuation than water from a deeper well [5]. However, any fluctuation of arsenic concentrations is likely to affect the cases and controls equally. Interviewer bias is less likely because the interviewers were unaware of the arsenic concentration levels of the participant’s usual drinking water source. Nevertheless, strength of this study is the study design, availability of individual arsenic exposure data, BMI and determination of risk at different arsenic concentration levels.

The findings of this study add to the evidence that chronic arsenic exposure is likely to contribute to poor nutritional status among women of 20–45 years.