PMID- 36976258
OWN - NLM
STAT- MEDLINE
DCOM- 20230330
LR  - 20230823
IS  - 1552-9924 (Electronic)
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 131
IP  - 3
DP  - 2023 Mar
TI  - The Folic Acid and Creatine Trial: Treatment Effects of Supplementation on 
      Arsenic Methylation Indices and Metabolite Concentrations in Blood in a 
      Bangladeshi Population.
PG  - 37015
LID - 10.1289/EHP11270 [doi]
LID - 037015
AB  - BACKGROUND: Chronic arsenic (As) exposure is a global environmental health issue. 
      Inorganic As (InAs) undergoes methylation to monomethyl (MMAs) and 
      dimethyl-arsenical species (DMAs); full methylation to DMAs facilitates urinary 
      excretion and is associated with reduced risk for As-related health outcomes. 
      Nutritional factors, including folate and creatine, influence one-carbon 
      metabolism, the biochemical pathway that provides methyl groups for As 
      methylation. OBJECTIVE: Our aim was to investigate the effects of supplementation 
      with folic acid (FA), creatine, or the two combined on the concentrations of As 
      metabolites and the primary methylation index (PMI: MMAs/InAs) and secondary 
      methylation index (SMI: DMAs/MMAs) in blood in Bangladeshi adults having a wide 
      range of folate status. METHODS: In a randomized, double-blinded, placebo 
      (PBO)-controlled trial, 622 participants were recruited independent of folate 
      status and assigned to one of five treatment arms: a) PBO (n = 102), b) 400 mug 
      FA/d (400FA; n = 153), c) 800 mug FA/d (800FA; n = 151), d) 3 g creatine/d 
      (creatine; n = 101), or e) 3 g creatine +  400 mug of FA/d (creatine +  400FA; n 
      = 103) for 12 wk. For the following 12 wk, half of the FA participants were 
      randomly switched to the PBO while the other half continued FA supplementation. 
      All participants received As-removal water filters at baseline. Blood As (bAs) 
      metabolites were measured at weeks 0, 1, 12, and 24. RESULTS: At baseline, 80.3% 
      (n = 489) of participants were folate sufficient ( >/= 9 nmol/L in plasma). In all 
      groups, bAs metabolite concentrations decreased, likely due to filter use; for 
      example, in the PBO group, blood concentrations of MMAs (bMMAs) (geometric 
      mean +/- geometric standard deviation) decreased from 3.55 +/- 1.89 mug/L at baseline 
      to 2.73 +/- 1.74 at week 1. After 1 wk, the mean within-person increase in SMI for 
      the creatine +  400FA group was greater than that of the PBO group (p = 0.05). 
      The mean percentage decrease in bMMAs between baseline and week 12 was greater 
      for all treatment groups compared with the PBO group [400FA: - 10.4 (95% CI: 
      - 11.9, - 8.75), 800FA: - 9.54 (95% CI: - 11.1, - 7.97), creatine: - 5.85 (95% 
      CI: - 8.59, - 3.03), creatine +  400FA: - 8.44 (95% CI: - 9.95, - 6.90), PBO: 
      - 2.02 (95% CI: - 4.03, 0.04)], and the percentage increase in blood DMAs (bDMAs) 
      concentrations for the FA-treated groups significantly exceeded that of PBO 
      [400FA: 12.8 (95% CI: 10.5, 15.2), 800FA: 11.3 (95% CI: 8.95, 13.8), creatine +  
      400FA: 7.45 (95% CI: 5.23, 9.71), PBO: - 0.15 (95% CI: - 2.85, 2.63)]. The mean 
      decrease in PMI and increase in SMI in all FA groups significantly exceeded PBO 
      (p < 0.05). Data from week 24 showed evidence of a reversal of treatment effects 
      on As metabolites from week 12 in those who switched from 800FA to PBO, with 
      significant decreases in SMI [ - 9.0% (95% CI: - 3.5, - 14.8)] and bDMAs [ - 5.9% 
      (95% CI: - 1.8, - 10.2)], whereas PMI and bMMAs concentrations continued to 
      decline [ - 7.16% (95% CI: - 0.48, - 14.3) and - 3.1% (95% CI: - 0.1, - 6.2), 
      respectively] for those who remained on 800FA supplementation. CONCLUSIONS: FA 
      supplementation lowered bMMAs and increased bDMAs in a sample of primarily 
      folate-replete adults, whereas creatine supplementation lowered bMMAs. Evidence 
      of the reversal of treatment effects on As metabolites following FA cessation 
      suggests short-term benefits of supplementation and underscores the importance of 
      long-term interventions, such as FA fortification. 
      https://doi.org/10.1289/EHP11270.
FAU - Abuawad, Ahlam K
AU  - Abuawad AK
AUID- ORCID: 0000-0002-7241-4574
AD  - Department of Environmental Health Sciences, Mailman School of Public Health, 
      Columbia University, New York, New York, USA.
FAU - Bozack, Anne K
AU  - Bozack AK
AD  - Department of Environmental Health Sciences, Mailman School of Public Health, 
      Columbia University, New York, New York, USA.
AD  - Division of Environmental Health Sciences, School of Public Health, University of 
      California, Berkeley, Berkeley, California, USA.
FAU - Navas-Acien, Ana
AU  - Navas-Acien A
AD  - Department of Environmental Health Sciences, Mailman School of Public Health, 
      Columbia University, New York, New York, USA.
FAU - Goldsmith, Jeff
AU  - Goldsmith J
AD  - Department of Biostatistics, Mailman School of Public Health, Columbia 
      University, New York, New York, USA.
FAU - Liu, Xinhua
AU  - Liu X
AD  - Department of Biostatistics, Mailman School of Public Health, Columbia 
      University, New York, New York, USA.
FAU - Hall, Megan N
AU  - Hall MN
AD  - Department of Epidemiology, Mailman School of Public Health, Columbia University, 
      New York, New York, USA.
FAU - Ilievski, Vesna
AU  - Ilievski V
AD  - Department of Environmental Health Sciences, Mailman School of Public Health, 
      Columbia University, New York, New York, USA.
FAU - Lomax-Luu, Angela M
AU  - Lomax-Luu AM
AD  - Department of Environmental Health Sciences, Mailman School of Public Health, 
      Columbia University, New York, New York, USA.
FAU - Parvez, Faruque
AU  - Parvez F
AD  - Department of Environmental Health Sciences, Mailman School of Public Health, 
      Columbia University, New York, New York, USA.
FAU - Shahriar, Hasan
AU  - Shahriar H
AD  - Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh.
FAU - Uddin, Mohammad N
AU  - Uddin MN
AD  - Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh.
FAU - Islam, Tariqul
AU  - Islam T
AD  - Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh.
FAU - Graziano, Joseph H
AU  - Graziano JH
AD  - Department of Environmental Health Sciences, Mailman School of Public Health, 
      Columbia University, New York, New York, USA.
FAU - Gamble, Mary V
AU  - Gamble MV
AUID- ORCID: 0000-0003-4169-1162
AD  - Department of Environmental Health Sciences, Mailman School of Public Health, 
      Columbia University, New York, New York, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01050556
GR  - R01 ES030945/ES/NIEHS NIH HHS/United States
GR  - R01 CA133595/CA/NCI NIH HHS/United States
GR  - Z01 ES090089/ImNIH/Intramural NIH HHS/United States
GR  - P30 ES009089/ES/NIEHS NIH HHS/United States
GR  - P42 ES010349/ES/NIEHS NIH HHS/United States
GR  - F31 ES032321/ES/NIEHS NIH HHS/United States
GR  - R25 GM062454/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
DEP - 20230328
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 935E97BOY8 (Folic Acid)
RN  - J1A23S0911 (indium arsenide)
RN  - N712M78A8G (Arsenic)
RN  - MU72812GK0 (Creatine)
SB  - IM
MH  - Adult
MH  - Humans
MH  - *Folic Acid
MH  - *Arsenic/urine
MH  - Creatine/therapeutic use/metabolism
MH  - Methylation
MH  - Dietary Supplements
PMC - PMC10045040
EDAT- 2023/03/29 06:00
MHDA- 2023/03/30 06:11
PMCR- 2023/03/28
CRDT- 2023/03/28 10:53
PHST- 2023/03/30 06:11 [medline]
PHST- 2023/03/28 10:53 [entrez]
PHST- 2023/03/29 06:00 [pubmed]
PHST- 2023/03/28 00:00 [pmc-release]
AID - EHP11270 [pii]
AID - 10.1289/EHP11270 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2023 Mar;131(3):37015. doi: 10.1289/EHP11270. Epub 2023 
      Mar 28.