Folic Acid Supplementation Lowers Blood Arsenic

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


Background: Chronic arsenic exposure currently affects < 100 mil- lion 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 methyl- ation 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 < g/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 concentra- tions, primarily by decreasing blood MMAs and increasing urinary DMAs. Therapeutic strategies to facilitate arsenic methylation, par- ticularly in populations with folate deficiency or hyperhomocys- teinemia or both, may lower blood arsenic concentrations and thereby contribute to the prevention of arsenic-induced illnesses. Am J Clin Nutr 2007;86:1202–9.

Key Words: Folic acid, folate deficiency, homocysteine, S-adenosylmethionine, SAM, creatinine, arsenic, monomethylar- sonic acid, dimethylarsinic acid, blood arsenic