The Folic Acid and Creatine Trial: Treatment Effects of Supplementation on Arsenic Methylation Indices and Metabolite Concentrations in Blood in a Bangladeshi Population.

Autor: Abuawad AK; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA., Bozack AK; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA.; Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, California, USA., Navas-Acien A; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA., Goldsmith J; Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York, USA., Liu X; Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York, USA., Hall MN; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA., Ilievski V; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA., Lomax-Luu AM; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA., Parvez F; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA., Shahriar H; Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh., Uddin MN; Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh., Islam T; Columbia University Arsenic Project in Bangladesh, Dhaka, Bangladesh., Graziano JH; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA., Gamble MV; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA.
Jazyk: angličtina
Zdroj: Environmental health perspectives [Environ Health Perspect] 2023 Mar; Vol. 131 (3), pp. 37015. Date of Electronic Publication: 2023 Mar 28.
DOI: 10.1289/EHP11270
Abstrakt: 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 μ g FA/d (400FA; n = 153 ), c ) 800 μ g FA/d (800FA; n = 151 ), d ) 3 g creatine/d (creatine; n = 101 ), or e ) 3 g  creatine + 400 μ g  of FA / d ( creatine + 400 FA ; 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 μ g / L at baseline to 2.73 ± 1.74 at week 1. After 1 wk, the mean within-person increase in SMI for the creatine + 400 FA 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 + 400 FA : - 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 + 400 FA : 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.
Databáze: MEDLINE
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