Folate and arsenic metabolism: A double-blind, placebo-controlled folic acid-supplementation trial in Bangladesh

Mary V. Gamble, Xinhua Liu, Habibul Ahsan, J. Richard Pilsner, Vesna Ilievski, Vesna Slavkovich, Faruque Parvez, Yu Chen, Diane Levy, Pam Factor-Litvak, Joseph H. Graziano

Research output: Contribution to journalArticle

Abstract

Background: Populations in South and East Asia and many other regions of the world are chronically exposed to arsenic-contaminated drinking water. To various degrees, ingested inorganic arsenic (InAs) is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) via folate-dependent one-carbon metabolism; impaired methylation is associated with adverse health outcomes. Consequently, folate nutritional status may influence arsenic methylation and toxicity. Objective: The objective of this study was to test the hypothesis that folic acid supplementation of arsenic-exposed adults would increase arsenic methylation. Design: Two hundred adults in a rural region of Bangladesh, previously found to have low plasma concentrations of folate (≤9 nmol/L) were enrolled in a randomized, double-blind, placebo-controlled folic acid-supplementation trial. Plasma concentrations of folate and homocysteine and urinary concentrations of arsenic metabolites were analyzed at baseline and after 12 wk of supplementation with folic acid at a dose of 400 μg/d or placebo. Results: The increase in the proportion of total urinary arsenic excreted as DMA in the folic acid group (72% before and 79% after supplementation) was significantly (P < 0.0001) greater than that in the placebo group, as was the reduction in the proportions of total urinary arsenic excreted as MMA (13% and 10%, respectively; P < 0.0001) and as InAs (15% and 11%, respectively; P < 0.001). Conclusions: These data indicate that folic acid supplementation to participants with low plasma folate enhances arsenic methylation. Because persons whose urine contains low proportions of DMA and high proportions of MMA and InAs have been reported to be at greater risk of skin and bladder cancers and peripheral vascular disease, these results suggest that folic acid supplementation may reduce the risk of arsenic-related health outcomes.

Original languageEnglish (US)
Pages (from-to)1093-1101
Number of pages9
JournalAmerican Journal of Clinical Nutrition
Volume84
Issue number5
StatePublished - Nov 1 2006

Fingerprint

Bangladesh
Arsenic
Folic Acid
Placebos
Cacodylic Acid
Methylation
Far East
Peripheral Vascular Diseases
Health
Homocysteine
Skin Neoplasms
Nutritional Status
Urinary Bladder Neoplasms
Drinking Water
Carbon
Urine

Keywords

  • Arsenic
  • Bangladesh
  • Creatine
  • Creatinine
  • Dimethylarsinic acid
  • Folate
  • Folate deficiency
  • Folic acid
  • Homocysteine
  • Hyperhomocysteinemia
  • Monomethylarsonic acid
  • One-carbon metabolism
  • S-adenosylmethionine
  • Vitamin B-12

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Gamble, M. V., Liu, X., Ahsan, H., Pilsner, J. R., Ilievski, V., Slavkovich, V., ... Graziano, J. H. (2006). Folate and arsenic metabolism: A double-blind, placebo-controlled folic acid-supplementation trial in Bangladesh. American Journal of Clinical Nutrition, 84(5), 1093-1101.

Folate and arsenic metabolism : A double-blind, placebo-controlled folic acid-supplementation trial in Bangladesh. / Gamble, Mary V.; Liu, Xinhua; Ahsan, Habibul; Pilsner, J. Richard; Ilievski, Vesna; Slavkovich, Vesna; Parvez, Faruque; Chen, Yu; Levy, Diane; Factor-Litvak, Pam; Graziano, Joseph H.

In: American Journal of Clinical Nutrition, Vol. 84, No. 5, 01.11.2006, p. 1093-1101.

Research output: Contribution to journalArticle

Gamble, MV, Liu, X, Ahsan, H, Pilsner, JR, Ilievski, V, Slavkovich, V, Parvez, F, Chen, Y, Levy, D, Factor-Litvak, P & Graziano, JH 2006, 'Folate and arsenic metabolism: A double-blind, placebo-controlled folic acid-supplementation trial in Bangladesh', American Journal of Clinical Nutrition, vol. 84, no. 5, pp. 1093-1101.
Gamble MV, Liu X, Ahsan H, Pilsner JR, Ilievski V, Slavkovich V et al. Folate and arsenic metabolism: A double-blind, placebo-controlled folic acid-supplementation trial in Bangladesh. American Journal of Clinical Nutrition. 2006 Nov 1;84(5):1093-1101.
Gamble, Mary V. ; Liu, Xinhua ; Ahsan, Habibul ; Pilsner, J. Richard ; Ilievski, Vesna ; Slavkovich, Vesna ; Parvez, Faruque ; Chen, Yu ; Levy, Diane ; Factor-Litvak, Pam ; Graziano, Joseph H. / Folate and arsenic metabolism : A double-blind, placebo-controlled folic acid-supplementation trial in Bangladesh. In: American Journal of Clinical Nutrition. 2006 ; Vol. 84, No. 5. pp. 1093-1101.
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abstract = "Background: Populations in South and East Asia and many other regions of the world are chronically exposed to arsenic-contaminated drinking water. To various degrees, ingested inorganic arsenic (InAs) is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) via folate-dependent one-carbon metabolism; impaired methylation is associated with adverse health outcomes. Consequently, folate nutritional status may influence arsenic methylation and toxicity. Objective: The objective of this study was to test the hypothesis that folic acid supplementation of arsenic-exposed adults would increase arsenic methylation. Design: Two hundred adults in a rural region of Bangladesh, previously found to have low plasma concentrations of folate (≤9 nmol/L) were enrolled in a randomized, double-blind, placebo-controlled folic acid-supplementation trial. Plasma concentrations of folate and homocysteine and urinary concentrations of arsenic metabolites were analyzed at baseline and after 12 wk of supplementation with folic acid at a dose of 400 μg/d or placebo. Results: The increase in the proportion of total urinary arsenic excreted as DMA in the folic acid group (72{\%} before and 79{\%} after supplementation) was significantly (P < 0.0001) greater than that in the placebo group, as was the reduction in the proportions of total urinary arsenic excreted as MMA (13{\%} and 10{\%}, respectively; P < 0.0001) and as InAs (15{\%} and 11{\%}, respectively; P < 0.001). Conclusions: These data indicate that folic acid supplementation to participants with low plasma folate enhances arsenic methylation. Because persons whose urine contains low proportions of DMA and high proportions of MMA and InAs have been reported to be at greater risk of skin and bladder cancers and peripheral vascular disease, these results suggest that folic acid supplementation may reduce the risk of arsenic-related health outcomes.",
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AU - Gamble, Mary V.

AU - Liu, Xinhua

AU - Ahsan, Habibul

AU - Pilsner, J. Richard

AU - Ilievski, Vesna

AU - Slavkovich, Vesna

AU - Parvez, Faruque

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AB - Background: Populations in South and East Asia and many other regions of the world are chronically exposed to arsenic-contaminated drinking water. To various degrees, ingested inorganic arsenic (InAs) is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) via folate-dependent one-carbon metabolism; impaired methylation is associated with adverse health outcomes. Consequently, folate nutritional status may influence arsenic methylation and toxicity. Objective: The objective of this study was to test the hypothesis that folic acid supplementation of arsenic-exposed adults would increase arsenic methylation. Design: Two hundred adults in a rural region of Bangladesh, previously found to have low plasma concentrations of folate (≤9 nmol/L) were enrolled in a randomized, double-blind, placebo-controlled folic acid-supplementation trial. Plasma concentrations of folate and homocysteine and urinary concentrations of arsenic metabolites were analyzed at baseline and after 12 wk of supplementation with folic acid at a dose of 400 μg/d or placebo. Results: The increase in the proportion of total urinary arsenic excreted as DMA in the folic acid group (72% before and 79% after supplementation) was significantly (P < 0.0001) greater than that in the placebo group, as was the reduction in the proportions of total urinary arsenic excreted as MMA (13% and 10%, respectively; P < 0.0001) and as InAs (15% and 11%, respectively; P < 0.001). Conclusions: These data indicate that folic acid supplementation to participants with low plasma folate enhances arsenic methylation. Because persons whose urine contains low proportions of DMA and high proportions of MMA and InAs have been reported to be at greater risk of skin and bladder cancers and peripheral vascular disease, these results suggest that folic acid supplementation may reduce the risk of arsenic-related health outcomes.

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KW - Folic acid

KW - Homocysteine

KW - Hyperhomocysteinemia

KW - Monomethylarsonic acid

KW - One-carbon metabolism

KW - S-adenosylmethionine

KW - Vitamin B-12

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