Folic acid and creatine as therapeutic approaches to lower blood arsenic: A randomized controlled trial

Brandilyn A. Peters, Megan N. Hall, Xinhua Liu, Faruque Parvez, Tiffany R. Sanchez, Alexander van Geen, Jacob L. Mey, Abu B. Siddique, Hasan Shahriar, Mohammad Nasir Uddin, Tariqul Islam, Olgica Balac, Vesna Ilievski, Pam Factor-Litvak, Joseph H. Graziano, Mary V. Gamble

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1294-1301
Number of pages8
JournalEnvironmental health perspectives
Volume123
Issue number12
DOIs
StatePublished - Dec 2015
Externally publishedYes

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Creatine
Arsenic
Folic Acid
Randomized Controlled Trials
Placebos
Therapeutics
Methylation
Drinking Water
Population

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Cite this

Folic acid and creatine as therapeutic approaches to lower blood arsenic : A randomized controlled trial. / Peters, Brandilyn A.; Hall, Megan N.; Liu, Xinhua; Parvez, Faruque; Sanchez, Tiffany R.; van Geen, Alexander; Mey, Jacob L.; Siddique, Abu B.; Shahriar, Hasan; Uddin, Mohammad Nasir; Islam, Tariqul; Balac, Olgica; Ilievski, Vesna; Factor-Litvak, Pam; Graziano, Joseph H.; Gamble, Mary V.

In: Environmental health perspectives, Vol. 123, No. 12, 12.2015, p. 1294-1301.

Research output: Contribution to journalArticle

Peters, BA, Hall, MN, Liu, X, Parvez, F, Sanchez, TR, van Geen, A, Mey, JL, Siddique, AB, Shahriar, H, Uddin, MN, Islam, T, Balac, O, Ilievski, V, Factor-Litvak, P, Graziano, JH & Gamble, MV 2015, 'Folic acid and creatine as therapeutic approaches to lower blood arsenic: A randomized controlled trial', Environmental health perspectives, vol. 123, no. 12, pp. 1294-1301. https://doi.org/10.1289/ehp.1409396
Peters, Brandilyn A. ; Hall, Megan N. ; Liu, Xinhua ; Parvez, Faruque ; Sanchez, Tiffany R. ; van Geen, Alexander ; Mey, Jacob L. ; Siddique, Abu B. ; Shahriar, Hasan ; Uddin, Mohammad Nasir ; Islam, Tariqul ; Balac, Olgica ; Ilievski, Vesna ; Factor-Litvak, Pam ; Graziano, Joseph H. ; Gamble, Mary V. / Folic acid and creatine as therapeutic approaches to lower blood arsenic : A randomized controlled trial. In: Environmental health perspectives. 2015 ; Vol. 123, No. 12. pp. 1294-1301.
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title = "Folic acid and creatine as therapeutic approaches to lower blood arsenic: A randomized controlled trial",
abstract = "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.",
author = "Peters, {Brandilyn A.} and Hall, {Megan N.} and Xinhua Liu and Faruque Parvez and Sanchez, {Tiffany R.} and {van Geen}, Alexander and Mey, {Jacob L.} and Siddique, {Abu B.} and Hasan Shahriar and Uddin, {Mohammad Nasir} and Tariqul Islam and Olgica Balac and Vesna Ilievski and Pam Factor-Litvak and Graziano, {Joseph H.} and Gamble, {Mary V.}",
year = "2015",
month = "12",
doi = "10.1289/ehp.1409396",
language = "English (US)",
volume = "123",
pages = "1294--1301",
journal = "Environmental Health Perspectives",
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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.

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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