Academic journal article Environmental Health Perspectives

Dietary Intake and Arsenic Methylation in a U.S. Population

Academic journal article Environmental Health Perspectives

Dietary Intake and Arsenic Methylation in a U.S. Population

Article excerpt

Millions of people worldwide are exposed to arsenic-contaminated drinking water, and ingestion of inorganic arsenic (InAs) has been associated with increased risks of cancer. The primary metabolic pathway of ingested InAs is methylation to monomethyl arsenic (MMA) and dimethyl arsenic (DMA). However, people vary greatly in the degree to which they methylate InAs, and recent evidence suggests that those who excrete high proportions of ingested arsenic as MMA are more susceptible than others to arsenic-caused cancer. To date, little is known about the factors that determine interindividual differences in arsenic methylation. In this study, we assessed the effect of diet on arsenic metabolism by measuring dietary intakes and urinary arsenic methylation patterns in 87 subjects from two arsenic-exposed regions in the western United States. Subjects in the lower quartile of protein intake excreted a higher proportion of ingested InAs as MMA (14.6 vs. 11.6%; p = 0.01) and a lower proportion as DMA (72.3 vs. 77.0%; p = 0.01) than did subjects in the upper quartile of protein intake. Subjects in the lower quartile of iron, zinc, and niacin intake also had higher urinary percent MMA and lower percent DMA levels than did subjects with higher intakes of these nutrients. These associations were also seen in multivariate regression analyses adjusted for age, sex, smoking, and total urinary arsenic. Given the previously reported links between high percent MMA and increased cancer risks, these findings are consistent with the theory that people with diets deficient in protein and other nutrients are more susceptible than others to arsenic-caused cancer. Key words: arsenic, drinking water, environmental health, metabolism, nutritional susceptibility. doi: 10.1289/ehp.7907 available via http://dx.doi.org/[Online 10 May 2005]

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Inorganic arsenic (InAs) occurs naturally in the groundwater of many parts of the world, and millions of people worldwide are exposed to drinking water containing this known carcinogen (Nordstrom 2002). Ingested arsenic causes cancers of the skin, bladder, and lung and has been associated with cancers of other organs [National Research Council (NRC) 1999, 2001]. The estimated risks associated with these exposures may be quite high. According to a subcommittee of the NRC, the cancer risks associated with lifetime exposures at the new U.S. standard of 10 [micro]g/L may be as high as 1 in 300 (NRC 1999, 2001). The U.S. drinking water standards for other carcinogens have been set at levels associated with cancer risks that are about 30-3,000 times lower (Smith et al. 2002). Importantly, the new U.S. standard for arsenic applies only to public water systems. Approximately 15% of the U.S. population obtain their water from private wells (U.S. Geological Survey 2004), and arsenic concentrations > 10 [micro]g/L have been documented in private wells throughout the United States (Ayotte et al. 2003; Steinmaus et al. 2003; Welch et al. 1999).

The primary metabolic pathway of ingested InAs in humans is methylation (Gebel 2002; Styblo et al. 2002; Vahter 2002). Ingested InAs is first methylated to monomethylarsonic acid (MMA5), which is reduced to monomethylarsonous acid (MMA3). MMA3 is then methylated to dimethylarsinic acid (DMA5), which is reduced to dimethylarsinous acid (DMA3). In humans, this process is not complete, and some arsenic remains as either InAs or MMA. Typically, ingested InAs is excreted as 10-20% InAs, 10-15% monomethyl arsenic (MMA), and 60-75% dimethyl arsenic (DMA) (Hopenhayn-Rich et al. 1993). However, large interindividual variations exist.

Until recently, methylation was thought to be primarily a detoxification pathway. This was based on the finding that MMA5 and DMA5--the most common forms of MMA and DMA found in exposed humans--are more readily excreted and less toxic than is InAs (Buchet et al. 1981; Gebel 2002; Hughes and Kenyon 1998; Moore et al. 1997). …

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