PMID- 30590411
OWN - NLM
STAT- MEDLINE
DCOM- 20191021
LR  - 20230214
IS  - 1938-3207 (Electronic)
IS  - 0002-9165 (Print)
IS  - 0002-9165 (Linking)
VI  - 109
IP  - 2
DP  - 2019 Feb 1
TI  - Folic acid supplementation enhances arsenic methylation: results from a folic 
      acid and creatine supplementation randomized controlled trial in Bangladesh.
PG  - 380-391
LID - 10.1093/ajcn/nqy148 [doi]
AB  - BACKGROUND: Arsenic exposure through drinking water persists in many regions. 
      Inorganic As (InAs) is methylated to monomethyl-arsenical species (MMAs) and 
      dimethyl-arsenical species (DMAs), facilitating urinary excretion. Arsenic 
      methylation is dependent on one-carbon metabolism, which is influenced by 
      nutritional factors such as folate and creatine. OBJECTIVE: This study 
      investigated the effects of folic acid (FA) and/or creatine supplementation on 
      the proportion of As metabolites in urine. DESIGN: In a 24-wk randomized, 
      double-blinded, placebo-controlled trial, 622 participants were assigned to 
      receive FA (400 or 800 mug per day), 3 g creatine per day, 400 mug FA + 3 g 
      creatine per day, or placebo. The majority of participants were folate 
      sufficient; all received As-removal water filters. From wk 12-24, half of the 
      participants receiving FA received placebo. RESULTS: Among groups receiving FA, 
      the mean decrease in ln(%InAs) and %MMAs and increase in %DMAs exceeded those of 
      the placebo group at wk 6 and 12 (P < 0.05). In the creatine group, the mean 
      decrease in %MMAs exceeded that of the placebo group at wk 6 and 12 (P < 0.05); 
      creatine supplementation did not affect change in %InAs or %DMAs. The decrease in 
      %MMAs at wk 6 and 12 was larger in the 800 microg FA than in the 400 microg FA group 
      (P = 0.034). There were no differences in treatment effects between the 400 microg FA 
      and creatine + FA groups. Data suggest a rebound in As metabolite proportions 
      after FA cessation; at wk 24, log(%InAs) and %DMAs were not significantly 
      different than baseline levels among participants who discontinued FA 
      supplementation. CONCLUSIONS: The results of this study confirm that FA 
      supplementation rapidly and significantly increases methylation of InAs to DMAs. 
      Further research is needed to understand the strong cross-sectional associations 
      between urinary creatinine and As methylation in previous studies. This trial was 
      registered at https://clinicaltrials.gov as NCT01050556.
FAU - Bozack, Anne K
AU  - Bozack AK
AD  - Departments of Environmental Health Sciences.
FAU - Hall, Megan N
AU  - Hall MN
AD  - Epidemiology.
FAU - Liu, Xinhua
AU  - Liu X
AD  - Biostatistics, Columbia University, New York, NY.
FAU - Ilievski, Vesna
AU  - Ilievski V
AD  - Departments of Environmental Health Sciences.
FAU - Lomax-Luu, Angela M
AU  - Lomax-Luu AM
AD  - Departments of Environmental Health Sciences.
FAU - Parvez, Faruque
AU  - Parvez F
AD  - Departments of Environmental Health Sciences.
FAU - Siddique, Abu B
AU  - Siddique AB
AD  - Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh.
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  - Departments of Environmental Health Sciences.
FAU - Gamble, Mary V
AU  - Gamble MV
AD  - Departments of Environmental Health Sciences.
LA  - eng
SI  - ClinicalTrials.gov/NCT01050556
GR  - F31 ES029019/ES/NIEHS NIH HHS/United States
GR  - R01 CA133595/CA/NCI NIH HHS/United States
GR  - P42 ES010349/ES/NIEHS NIH HHS/United States
GR  - T32 ES007322/ES/NIEHS NIH HHS/United States
GR  - TL1 TR001875/TR/NCATS NIH HHS/United States
GR  - R01 ES017875/ES/NIEHS NIH HHS/United States
GR  - P30 ES009089/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Am J Clin Nutr
JT  - The American journal of clinical nutrition
JID - 0376027
RN  - 0 (Arsenicals)
RN  - 0 (Water Pollutants, Chemical)
RN  - 12001-76-2 (Vitamin B Complex)
RN  - 935E97BOY8 (Folic Acid)
RN  - MU72812GK0 (Creatine)
RN  - N712M78A8G (Arsenic)
SB  - IM
MH  - Adult
MH  - Arsenic/*metabolism
MH  - Arsenicals/*metabolism
MH  - Bangladesh
MH  - Creatine/*pharmacology
MH  - Cross-Sectional Studies
MH  - *Dietary Supplements
MH  - Environmental Exposure
MH  - Female
MH  - Folic Acid/*pharmacology/therapeutic use
MH  - Folic Acid Deficiency/complications/drug therapy
MH  - Humans
MH  - Inactivation, Metabolic
MH  - Male
MH  - Mercury Poisoning/metabolism/prevention & control
MH  - Methylation
MH  - Middle Aged
MH  - Nutrition Therapy
MH  - Vitamin B Complex/*pharmacology/therapeutic use
MH  - Water Pollutants, Chemical
MH  - Young Adult
PMC - PMC6367980
EDAT- 2018/12/28 06:00
MHDA- 2019/10/23 06:00
PMCR- 2020/02/01
CRDT- 2018/12/28 06:00
PHST- 2017/12/14 00:00 [received]
PHST- 2018/06/19 00:00 [accepted]
PHST- 2018/12/28 06:00 [pubmed]
PHST- 2019/10/23 06:00 [medline]
PHST- 2018/12/28 06:00 [entrez]
PHST- 2020/02/01 00:00 [pmc-release]
AID - S0002-9165(22)03101-X [pii]
AID - nqy148 [pii]
AID - 10.1093/ajcn/nqy148 [doi]
PST - ppublish
SO  - Am J Clin Nutr. 2019 Feb 1;109(2):380-391. doi: 10.1093/ajcn/nqy148.