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. 2008 Mar;116(3):315-21.
doi: 10.1289/ehp.10639.

Nutritional status has marginal influence on the metabolism of inorganic arsenic in pregnant Bangladeshi women

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Nutritional status has marginal influence on the metabolism of inorganic arsenic in pregnant Bangladeshi women

Li Li et al. Environ Health Perspect. 2008 Mar.

Abstract

Background: The interindividual variation in metabolism of inorganic arsenic (iAs), involving methylation via one-carbon metabolism, has been well documented, but the reasons remain unclear.

Objectives: In this population-based study we aimed to elucidate the effect of nutrition on As methylation among women in Matlab, Bangladesh, where people are chronically exposed to iAs via drinking water.

Methods: We studied effects of macronutrient status using body mass index (BMI) among 442 women in early pregnancy (gestational week 8), and effects of micronutrient status (plasma folate, vitamin B12, zinc, ferritin, and selenium) among 753 women at gestational week 14. Arsenic metabolites in urine were measured by HPLC combined with hydride generation inductively coupled plasma mass spectrometry.

Results: The median concentration of As in urine was 97 microg/L (range, 5-1,216 microg/L, adjusted by specific gravity). The average proportions of iAs, monomethylarsonic acid, and dimethylarsinic acid in urine in gestational week 8 were 15%, 11%, and 74%, respectively. Thus, the women had efficient As methylation in spite of being poorly nourished (one-third had BMIs < 18.5 kg/m2) and having elevated As exposure, both of which are known to decrease As methylation. The metabolism of iAs was only marginally influenced by micronutrient status, probably because women, especially in pregnancy and with low folate intake, have an efficient betaine-mediated remethylation of homocysteine, which is essential for an efficient As methylation.

Conclusions: In spite of the high As exposure and prevalent malnutrition, overall As methylation in women in early pregnancy was remarkably efficient. The As exposure level had the greatest impact on As methylation among the studied factors.

Keywords: arsenic; metabolite; methylation; nutrition; pregnant women; urine.

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Figures

Figure 1
Figure 1
Overview of one-carbon metabolism and the methylation of As. Abbreviations: 5,10-CH2-THF, methylene tetrahydrofolate; AS3MT, As methyltransferase; DMG, dimethylglycine; GAA, guanidinoacetate; MTHFR, 5,10-CH2-THF reductase; SAH, S-adenosylhomocysteine; THF, tetrahydrofolate. Methionine, which originates from dietary protein and tissue protein, is activated by methionine adenosyltransferase to form SAM, which provides methyl groups for most methylation reactions in the body (e.g., methylation of DNA, GAA to creatine, and iAs to MMA and DMA). Methyltransferases are required for the methylation reactions, in which SAH is formed. SAH is hydrolyzed to homocysteine, which is used either for regeneration of methionine or for glutathione (GSH) biosynthesis in a transsulfuration pathway. In one methionine regeneration pathway, the methyl group is transferred to homocysteine from 5-CH3-THF and catalyzed by vitamin B12. In the alternate pathway, the methyl group is transferred from betaine and catalyzed by betaine:homocysteine methyltransferase (BHMT).
Figure 2
Figure 2
Selection of participants to studies of effects of macronutrient and micronutrient status on As metabolism.
Figure 3
Figure 3
Frequency distribution of As metabolites in urine, demonstrating the interindividual variability in As metabolism among 442 pregnant women in GW8.

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