Folic Acid and Creatine as Therapeutic Approaches to Lower Blood Arsenic: A Randomized Controlled Trial
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
Environmental health perspectives · 78 citations
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- National Institutes of Health
- Government
- National Cancer Institute
- Government
- National Institute of Environmental Health Sciences
- Government
- NIEHS NIH HHS
- Government
- NCI NIH HHS
- Grants
- National Cancer Institute (R01 CA133595); National Institute of Environmental Health Sciences (P30 ES009089); National Institute of Environmental Health Sciences (P42 ES10349); National Institute of Environmental Health Sciences (R00 ES018890); National Institute of Environmental Health Sciences (P42ES010349); National Institute of Environmental Health Sciences (P30-ES09089); National Institutes of Health (R01CA133595); National Institutes of Health (P42 ES 10349); National Institutes of Health (P30 ES 09089)
Based on 5 listed funder(s).
Publication
- Published
- 2015-05-15 · Environ Health Perspect · vol. 123 · issue 12 · pp. 1294–1301
- Publisher
- National Institute of Environmental Health Sciences
- Cited
- 95 citations · more than 99% of similar papers · 11.3× the field average
- Impact
- Top 10% most cited in its field
- References
- 38 works
- Access
- Open access (journal) · PUBLIC-DOMAIN
- Research areas
- Arsenic contamination and mitigation · Folate and B Vitamins Research · Heavy Metal Exposure and Toxicity
- Keywords
- Creatine, Placebo, Medicine, Creatinine, Population, Randomized controlled trial, Internal medicine, Urine, Physiology, Gastroenterology, Environmental health, Pathology
- MeSH
- humans, arsenic, creatine, creatinine, folic acid, water pollutants, chemical, water purification, methylation, dietary supplements, adult, aged, middle aged, bangladesh, female, male, drinking water
16 authors
From US
- Brandilyn A. PetersCenter for Environmental Health
- Megan N. Hall
- Xinhua LiuColumbia University
- Faruque ParvezCenter for Environmental Health
- Tiffany R. SanchezCenter for Environmental Health
- Alexander van GeenLamont-Doherty Earth Observatory; Columbia University
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC0).
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