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American Journal of Clinical Nutrition, Vol. 86, No. 4, 1202-1209, October 2007
© 2007 American Society for Nutrition

ORIGINAL RESEARCH COMMUNICATION

Folic acid supplementation lowers blood arsenic1,2,3

Mary V Gamble, Xinhua Liu, Vesna Slavkovich, J Richard Pilsner, Vesna Ilievski, Pam Factor-Litvak, Diane Levy, Shafiul Alam, Mominul Islam, Faruque Parvez, Habibul Ahsan and Joseph H Graziano

1 From the Departments of Environmental Health Sciences (MVG, VS, JRP, VI, FP, and JHG), Biostatistics (XL and DL), and Epidemiology (PF-L and HA), Mailman School of Public Health, Columbia University, New York, NY; the Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh (SA and MI); the Department of Health Studies, University of Chicago, Chicago, IL (HA); and the Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY (JHG)

Background: Chronic arsenic exposure currently affects >100 million persons worldwide. Methylation of ingested inorganic arsenic (InAs) to monomethylarsonic (MMAs) and dimethylarsinic (DMAs) acids relies on folate-dependent one-carbon metabolism and facilitates urinary arsenic elimination.

Objective: We hypothesized that folic acid supplementation to arsenic-exposed Bangladeshi adults would increase arsenic methylation and thereby lower total blood arsenic.

Design: In this randomized, double-blind, placebo-controlled trial, we evaluated blood concentrations of total arsenic, InAs, MMAs, and DMAs in 130 participants with low plasma folate (<9 nmol/L) before and after 12 wk of supplementation with folic acid (400 µg/d) or placebo.

Results: MMAs in blood was reduced by a mean ± SE of 22.24 ± 2.86% in the folic acid supplementation group and by 1.24 ± 3.59% in the placebe group (P < 0.0001). There was no change in DMAs in blood; DMAs is rapidly excreted in urine as evidenced by an increase in urinary DMAs (P = 0.0099). Total blood arsenic was reduced by 13.62% in the folic acid supplementation group and by 2.49% in the placebo group (P = 0.0199).

Conclusions: Folic acid supplementation to participants with low plasma concentrations of folate lowered blood arsenic concentrations, primarily by decreasing blood MMAs and increasing urinary DMAs. Therapeutic strategies to facilitate arsenic methylation, particularly in populations with folate deficiency or hyperhomocysteinemia or both, may lower blood arsenic concentrations and thereby contribute to the prevention of arsenic-induced illnesses.

Key Words: Folic acid • folate deficiency • homocysteine • S-adenosylmethionine • SAM • creatinine • arsenic • monomethylarsonic acid • dimethylarsinic acid • blood arsenic






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