TY - JOUR
T1 - Folic acid and creatine as therapeutic approaches to lower blood arsenic
T2 - A randomized controlled trial
AU - Peters, Brandilyn A.
AU - Hall, Megan N.
AU - Liu, Xinhua
AU - Parvez, Faruque
AU - Sanchez, Tiffany R.
AU - van Geen, Alexander
AU - Mey, Jacob L.
AU - Siddique, Abu B.
AU - Shahriar, Hasan
AU - Uddin, Mohammad Nasir
AU - Islam, Tariqul
AU - Balac, Olgica
AU - Ilievski, Vesna
AU - Factor-Litvak, Pam
AU - Graziano, Joseph H.
AU - Gamble, Mary V.
N1 - Publisher Copyright:
© 2015 Public Health Services, US Dept of Health and Human Services. All rights reserved.
PY - 2015/12
Y1 - 2015/12
N2 - BACKGROUND: The World Health Organization estimates that > 140 million people worldwide are exposed to arsenic (As)–contaminated drinking water. As undergoes biologic methylation, which facilitates renal As elimination. In folate-deficient individuals, this process is augmented by folic acid (FA) supplementation, thereby lowering blood As (bAs). Creatinine concentrations in urine are a robust predictor of As methylation patterns. Although the reasons for this are unclear, creatine synthesis is a major consumer of methyl donors, and this synthesis is down-regulated by dietary/supplemental creatine. OBJECTIVES: Our aim was to determine whether 400 or 800 μg FA and/or creatine supplementation lowers bAs in an As-exposed Bangladeshi population. METHODS: We conducted a clinical trial in which 622 participants were randomized to receive 400 μg FA, 800 μg FA, 3 g creatine, 3 g creatine +400 μg FA, or placebo daily. All participants received an As-removal filter on enrollment, and were followed for 24 weeks. After the 12th week, half of the two FA groups were switched to placebo to evaluate post-treatment bAs patterns. RESULTS: Linear models with repeated measures indicated that the decline in ln(bAs) from baseline in the 800-μg FA group exceeded that of the placebo group (weeks 1–12: β = –0.09, 95% CI: –0.18, –0.01; weeks 13–24: FA continued: β = –0.12, 95% CI: –0.24, –0.00; FA switched to placebo: β = –0.14, 95% CI: –0.26, –0.02). There was no rebound in bAs related to cessation of FA supplementation. Declines in bAs observed in the remaining treatment arms were not significantly different from those of the placebo group. CONCLUSIONS: In this mixed folate-deficient/replete study population, 12- and 24-week treatment with 800 μg (but not 400 μg) FA lowered bAs to a greater extent than placebo; this was sustained 12 weeks after FA cessation. In future studies, we will evaluate whether FA and/or creatine altered As methylation profiles.
AB - BACKGROUND: The World Health Organization estimates that > 140 million people worldwide are exposed to arsenic (As)–contaminated drinking water. As undergoes biologic methylation, which facilitates renal As elimination. In folate-deficient individuals, this process is augmented by folic acid (FA) supplementation, thereby lowering blood As (bAs). Creatinine concentrations in urine are a robust predictor of As methylation patterns. Although the reasons for this are unclear, creatine synthesis is a major consumer of methyl donors, and this synthesis is down-regulated by dietary/supplemental creatine. OBJECTIVES: Our aim was to determine whether 400 or 800 μg FA and/or creatine supplementation lowers bAs in an As-exposed Bangladeshi population. METHODS: We conducted a clinical trial in which 622 participants were randomized to receive 400 μg FA, 800 μg FA, 3 g creatine, 3 g creatine +400 μg FA, or placebo daily. All participants received an As-removal filter on enrollment, and were followed for 24 weeks. After the 12th week, half of the two FA groups were switched to placebo to evaluate post-treatment bAs patterns. RESULTS: Linear models with repeated measures indicated that the decline in ln(bAs) from baseline in the 800-μg FA group exceeded that of the placebo group (weeks 1–12: β = –0.09, 95% CI: –0.18, –0.01; weeks 13–24: FA continued: β = –0.12, 95% CI: –0.24, –0.00; FA switched to placebo: β = –0.14, 95% CI: –0.26, –0.02). There was no rebound in bAs related to cessation of FA supplementation. Declines in bAs observed in the remaining treatment arms were not significantly different from those of the placebo group. CONCLUSIONS: In this mixed folate-deficient/replete study population, 12- and 24-week treatment with 800 μg (but not 400 μg) FA lowered bAs to a greater extent than placebo; this was sustained 12 weeks after FA cessation. In future studies, we will evaluate whether FA and/or creatine altered As methylation profiles.
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U2 - 10.1289/ehp.1409396
DO - 10.1289/ehp.1409396
M3 - Article
C2 - 25978852
AN - SCOPUS:84949238553
SN - 0091-6765
VL - 123
SP - 1294
EP - 1301
JO - Environmental Health Perspectives
JF - Environmental Health Perspectives
IS - 12
ER -
