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Research Detail

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Lydia B. Zablotska
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA

Yu Chen
Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA

Joseph H. Graziano
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA

Faruque Parvez
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA

Alexander van Geen
4Lamont-Doherty Earth Observatory of Columbia University, New York, New York, USA

Geoffrey R. Howe
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA

Habibul Ahsan
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA; 5Department of Health Studies, 6Department of Medicine, 7Department of Human Genetics, and 8Cancer Research Center, The University of Chicago, Chicago, Illinois, USA

Background

An estimated 25–40 million of the 127 million people of Bangladesh have been exposed to high levels of naturally occurring arsenic from drinking groundwater. The mitigating effects of diet on arsenic-related premalignant skin lesions are largely unknown.

Objectives

The purpose of this study was to clarify the effects of the vitamin B group (thiamin, riboflavin, niacin, pyridoxine, and cobalamin) and antioxidants (vitamins A, C, and E) on arsenic-related skin lesions.

Methods

We performed a cross-sectional study using baseline data from the Health Effects of Arsenic Longitudinal Study (HEALS), 2000–2002, with individual-level, time-weighted measures of arsenic exposure from drinking water. A total of 14,828 individuals meeting a set of eligibility criteria were identified among 65,876 users of all 5,996 tube wells in the 25-km2 area of Araihazar, Bangladesh; 11,746 were recruited into the study. This analysis is based on 10,628 subjects (90.5%) with nonmissing dietary data. Skin lesions were identified according to a structured clinical protocol during screening and confirmed with further clinical review.

Results

Riboflavin, pyridoxine, folic acid, and vitamins A, C, and E significantly modified risk of arsenic-related skin lesions. The deleterious effect of ingested arsenic, at a given exposure level, was significantly reduced (ranging from 46% reduction for pyridoxine to 68% for vitamin C) for persons in the highest quintiles of vitamin intake.

Conclusions

Intakes of B-vitamins and antioxidants, at doses greater than the current recommended daily amounts for the country, may reduce the risk of arsenic-related skin lesions in Bangladesh.

  Antioxidants, Arsenic, Bangladesh, B vitamins, Skin lesions. Environ Health Perspect
  In Bangladesh.
  
  
  Resource Development and Management
  Arsenic

The U.S. Department of Agriculture (USDA 2006) and Indian nutritional tables (Gopalan et al. 1996) were used to estimate the consumption of various vitamins and antioxidants. Here, using the baseline data of the HEALS cohort, we report the results of analyses aimed at clarifying the effects of the vitamin B group, including thiamin (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), pyridoxine (vitamin B6), cobalamin (vitamin B12), and folic acid and antioxidants (vitamins A, C, and E) on the relationship between arsenic exposure and skin lesions.

The detailed description of the study methods and participants of the HEALS cohort analyzed here has been published previously. In brief, we identified and tested all 5,996 tube wells in the 25-km2 area of Araihazar, Bangladesh, and proceeded to recruit eligible cohort members from their 65,876 users. A total of 14,828 individuals met the following eligibility criteria: married and ≥ 18 years of age; resident in the study area for at least 5 years before recruitment; and user of one of the study wells for at least 3 years. Nineteen percent of the eligible individuals (n = 2,778) were not at home during study visits. Of the 12,050 individuals who were available and approached, 11,746 (97.5% response rate) were recruited to the cohort between October 2000 and May 2002. Informed consent was obtained from each eligible respondent who agreed to participate in the study. The study protocol and field procedures were approved by the Columbia University Institutional Review Board and by the Ethical Committee of the Bangladesh Medical Research Council.

Measurement of arsenic exposure

Water samples from all tube wells were analyzed for arsenic concentrations by the graphite furnace arsenic absorption method, as described previously. Detailed information about water consumption in the preceding years from questionnaires was used to construct the individual-level, time-weighted arsenic (TWA) exposure measure, taking into account both arsenic concentration and duration of water drinking from the index tube well. Thus, TWA (in micrograms per liter) = ∑ CiTi/∑Ti, where Ci and Ti denote the well arsenic concentration and drinking duration for the ith well, respectively.

All HEALS participants provided urine samples, which were used to estimate total urinary arsenic concentration by the graphite furnace arsenic absorption method, as described previously. Urinary creatinine was analyzed using a method based on the Jaffe reaction.

Measurement of vitamins and antioxidants

The baseline interview collected information on diet using a semiquantitative 39-item FFQ designed to assess the long-term usual diet of cohort participants and described in detail elsewhere. Briefly, HEALS investigators, with help from local nutrition experts, first identified all the food items available at the village market in the study area. The FFQ was finalized after pilot testing to include common food items. Food items with intake frequencies less than once per month during the past year were deemed to be insignificant. We are confident that the food list covers > 90% of the typical daily diet in the study population, because the development of the food list was based on extensive pilot work and the diet in rural Bangladesh is relatively homogeneous and simple. Food diversity is limited by the low availability of tillable land. The average diet is almost entirely cereal-based, comprising very few highly processed food products. The use of dietary/nutritional supplements is rare in Bangladesh. The reasonable average daily intakes of energy computed from both the FFQ and a food diary (FD) gave reassurance on this aspect. Extensive work was done to assess the validity of the data collected from the FFQ, including two 7-day FDs for 189 randomly selected study subjects. The latter showed moderately good correlations for B vitamins with the FFQ; for example, energy-adjusted correlation coefficients with correction for within-individual variation were 0.46 for riboflavin, 0.39 for niacin, and 0.57 for cobalamin. Although large seasonal variations between the two FDs were observed for vitamins A and C, overall the FFQ was deemed an adequate tool to capture long-term intakes of common foods and nutrients in this population.

  Environmental Health Perspective; Vol. 116, No. 8
  
Funding Source:
1.   Budget:  
  

The results of this study strongly suggest that consumption of foods rich in vitamins such as riboflavin; pyridoxine; vitamins A, C, and E; and folic acid may influence the relationship between exposure to water arsenic and subsequent risk of skin lesions. Those in the highest quintiles of consumption had significant reductions in risks for skin lesions associated with arsenic exposure. The observed modifying effects were associated with consumption of nutrients at doses that are higher than the current recommended daily amounts for the country. These findings support the hypothesis that nutrients relevant to arsenic metabolism and antioxidant nutrients may modify the risk of arsenic-related skin lesions in Bangladesh. Future studies looking at that influence of micronutrients on risk of incident arsenicrelated skin lesions are necessary to clarify the nature of the association. Intervention studies are also needed to determine whether dietary supplementation may mediate health effects of arsenic exposure

  Journal
  


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