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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA.
authors.forename: Brandilyn A
authors.initials: BA
authors.lastname: Peters
authors.forename: Megan N
authors.initials: MN
authors.lastname: Hall
authors.forename: Xinhua
authors.initials: X
authors.lastname: Liu
authors.forename: Faruque
authors.initials: F
authors.lastname: Parvez
authors.forename: Tiffany R
authors.initials: TR
authors.lastname: Sanchez
authors.forename: Alexander
authors.initials: A
authors.lastname: van Geen
authors.forename: Jacob L
authors.initials: JL
authors.lastname: Mey
authors.forename: Abu B
authors.initials: AB
authors.lastname: Siddique
authors.forename: Hasan
authors.initials: H
authors.lastname: Shahriar
authors.forename: Mohammad Nasir
authors.initials: MN
authors.lastname: Uddin
authors.forename: Tariqul
authors.initials: T
authors.lastname: Islam
authors.forename: Olgica
authors.initials: O
authors.lastname: Balac
authors.forename: Vesna
authors.initials: V
authors.lastname: Ilievski
authors.forename: Pam
authors.initials: P
authors.lastname: Factor-Litvak
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Graziano
authors.forename: Mary V
authors.initials: MV
authors.lastname: Gamble
mesh_terms: D000328:Adult; D000368:Aged; D001151:Arsenic / Q000097:blood* / Q000633:toxicity; D001459:Bangladesh; D003401:Creatine / Q000008:administration & dosage*; D003404:Creatinine / Q000652:urine; D019587:Dietary Supplements; D060766:Drinking Water; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D014874:Water Pollutants, Chemical / Q000097:blood* / Q000633:toxicity; D018508:Water Purification
chemical_list: D060766:Drinking Water; D014874:Water Pollutants, Chemical; D005492:Folic Acid; D003404:Creatinine; D003401:Creatine; D001151:Arsenic