Folic acid supplementation lowers blood arsenic

Abstract

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 microg/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.

FIGURE 1

Mean (±SE) percentage change in total blood arsenic from baseline after supplementation for 12 wk with folic acid ( ) (n = 68) or placebo (□) (n = 62) (P = 0.02).

FIGURE 2

Baseline blood concentrations of monomethylarsonic acid (MMAs; μg/L) for each participant (♦) in the folic acid (A) and placebo (B) groups. — (smoothed by sorting on baseline MMAs), the range of MMAs at baseline (1–15 μg/L); , each participant’s corresponding blood MMAs after the 12-wk intervention. Rising and falling vertical bars indicate each participant’s increase or decrease, respectively, in blood MMAs from that participant’s baseline.

FIGURE 3

Mean (±SD) percentage of arsenic in blood and in urine at baseline in 130 participants. □, the percentage of total urinary arsenic present as inorganic arsenic (InAs), monomethylarsonic acid (MMAs), and dimethylarsinic acid (DMAs) in urine; , the percentage of total blood arsenic as InAs, MMAs, and DMAs in blood. Plotted values are the mean ± SD for 130 participants at baseline.