1056 VOLUME 116 | NUMBER 8 | August 2008 • Environmental Health Perspectives Research | Environmental Medicine Inorganic arsenic occurring in various forms in the environment has been classified as a definite human carcinogen (group 1) since 1979 (International Agency for Research on Cancer 1980). Numerous studies conducted in Taiwan and South America found that exposure to inorganic arsenic from drinking water is associated with cancers of the bladder, kidneys, skin, and other organs and tissues (Cantor 1997; Ferreccio et al. 2000). Similar to Taiwan, several countries in South Asia have high levels of naturally occur- ring arsenic in groundwater. In the early 1970s, the government of Bangladesh, with the support and financing of the United Nations Children’s Fund, promoted the dig- ging of the tube wells to provide clean drink- ing water. In the late 1990s, evidence indicated that the groundwater, the main source of drinking water in Bangladesh, is contaminated by naturally occurring arsenic in 59 of the 64 districts of the country. An estimated 25–40 million of Bangladesh’s 127 million people have been exposed to levels frequently above the national limit of 50 ppb and often reaching levels as high as 800 ppb (British Geological Survey 2006). Several studies have shown convincing evi- dence of the association between drinking arsenic-rich water and skin lesions, which are recognized as precursors of nonmelanoma skin cancer (Ahsan et al. 2006b; Guha Mazumder et al. 1998; Tondel et al. 1999). Recent studies conducted in South Asia have raised the possi- bility that antioxidants may modify the effects of water arsenic on the risk of skin lesions (Hsueh et al. 1995; Vahter 2000). Folate and cobalamin (vitamin B 12 ) have been suggested to play an important role in the detoxification of ingested arsenic (Gamble et al. 2005b; Mitra et al. 2004; National Research Council 1999). Specifically, methylation of arsenic is a folic acid–dependent reaction catalyzed by a cobalamin-dependent enzyme (Gamble et al. 2005b; Zakharyan and Aposhian 1999). Steinmaus et al. (2005) showed that consump- tion of high levels of niacin (vitamin B 3 ) was associated with arsenic methylation. Other studies showed some evidence that anti- oxidants such as vitamin A also play a role in diminishing arsenic toxicity (Chattopadhyay et al. 2002; Hsueh et al. 1995; Roychowdhury et al. 2003; Styblo and Thomas 2001). To date, few studies have evaluated the effects of diet specific to Bangladesh on the relationship between arsenic exposure from drinking water and skin lesions. McCarty et al. (2006) reported a significantly reduced risk associated with intake of fruits and canned goods, but were not able to assess the effects of individual food compounds. The Health Effects of Arsenic Longitudinal Study (HEALS) was established to examine the health effects of arsenic exposure in Bangladesh. It is a population-based prospective cohort study in Araihazar, Bangladesh, with individ- ual-level water arsenic measurements. We recently reported an increased dose-related risk of skin lesions in relation to arsenic exposure in this cohort (Ahsan et al. 2006b). As part of the investigation, we collected detailed information about the daily diet of all participants, using a food frequency questionnaire (FFQ) developed specifically for this population. The U.S. Department of Agriculture (USDA 2006) and Indian nutritional tables (Gopalan et al. 1996) were used to estimate the consumption of var- ious vitamins and antioxidants. Here, using the baseline data of the HEALS cohort, we report the results of analyses aimed at clari- fying the effects of the vitamin B group, including thiamin (vitamin B 1 ), riboflavin (vitamin B 2 ), niacin (vitamin B 3 ), pyridoxine (vitamin B 6 ), cobalamin (vitamin B 12 ), and folic acid and antioxidants (vitamins A, C, and E) on the relationship between arsenic exposure and skin lesions. Materials and Methods The detailed description of the study methods and participants of the HEALS cohort ana- lyzed here has been published previously (Ahsan et al. 2006a, 2006b; Parvez et al. 2006). In brief, we identified and tested all 5,996 tube wells in the 25-km 2 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 Address correspondence to H. Ahsan, The University of Chicago, 5841 South Maryland Ave., Suite N102, Chicago, IL 60637 USA. Telephone: (773) 834-9956. Fax: (773) 702-0139. E-mail: habib@uchicago.edu This work was supported by National Institutes of Health grants 2P42 ES10349-06, P30ES09089, R01CA107431, and RO1CA102484. The authors declare they have no competing financial interests. Received 25 July 2007; accepted 13 April 2008. Protective Effects of B Vitamins and Antioxidants on the Risk of Arsenic-Related Skin Lesions in Bangladesh Lydia B. Zablotska, 1 Yu Chen, 2 Joseph H. Graziano, 3 Faruque Parvez, 3 Alexander van Geen, 4 Geoffrey R. Howe, 1 and Habibul Ahsan 1,5,6,7,8 1 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA; 2 Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA; 3 Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA; 4 Lamont-Doherty Earth Observatory of Columbia University, New York, New York, USA; 5 Department of Health Studies, 6 Department of Medicine, 7 Department of Human Genetics, and 8 Cancer 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-km 2 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 clini- cal 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 per- sons 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. KEY WORDS: antioxidants, arsenic, Bangladesh, B vitamins, skin lesions. Environ Health Perspect 116:1056–1062 (2008). doi:10.1289/ehp.10707 available via http://dx.doi.org/ [Online 16 April 2008]