The Folic Acid and Creatine Trial: Treatment Effects of Supplementation on Arsenic Methylation Indices and Metabolite Concentrations in Blood in a Bangladeshi Population
Abuawad AK, Bozack AK, Navas-Acien A, Goldsmith J, Liu X, Hall MN, Ilievski V, Lomax-Luu AM, Parvez F, Shahriar H, Uddin MN, Islam T, Graziano JH, Gamble MV
Environmental health perspectives · 11 citas
Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- National Institutes of Health
- Gobierno
- National Cancer Institute
- Gobierno
- National Institute of General Medical Sciences
- Gobierno
- National Institute of Environmental Health Sciences
- Gobierno
- NCI NIH HHS
- Gobierno
- NIEHS NIH HHS
- Gobierno
- NIGMS NIH HHS
- Gobierno
- Intramural NIH HHS
- Subvenciones
- National Institute of Environmental Health Sciences (R01 ES030945); National Cancer Institute (R01 CA133595); National Institute of Environmental Health Sciences (P42ES010349); National Institute of General Medical Sciences (R25GM062454); National Institute of Environmental Health Sciences (Z01ES090089); National Institute of Environmental Health Sciences (F31 ES032321); National Institutes of Health (R01CA133595); National Institutes of Health (R01ES030945); National Institutes of Health (P42 ES010349); National Institute of Environmental Health Sciences (P30ES009089)
Según 8 financiadores declarados.
Publicación
- Publicado
- 2023-03-01 · Environ Health Perspect · vol. 131 · número 3 · pág. 37015
- Editorial
- National Institute of Environmental Health Sciences
- Citado
- 15 citas · más que el 75% de estudios similares · 1.2× el promedio de su campo
- Referencias
- 54 trabajos
- Acceso
- Acceso abierto (revista) · PUBLIC-DOMAIN
- Áreas de investigación
- Arsenic contamination and mitigation · Heavy Metal Exposure and Toxicity · Folate and B Vitamins Research
- Palabras clave
- chronic arsenic exposure, arsenic methylation, folic acid supplementation, creatine supplementation, one-carbon metabolism, arsenic metabolites, monomethylarsonic acid, dimethylarsinic acid, Bangladeshi adults, folate status, dietary arsenic intake, urinary arsenic
- MeSH
- humans, arsenicals, arsenic, indium, creatine, folic acid, methylation, dietary supplements, adult
14 autores
- Ahlam Kifah Abuawad🇺🇸Columbia University
- Anne K. Bozack🇺🇸Columbia University; University of California, Berkeley
- Ana Navas‐Acién🇺🇸Columbia University
- Jeff Goldsmith🇺🇸Columbia University
- Xinhua Liu🇺🇸Columbia University
- Megan N. Hall🇺🇸Columbia University
- Vesna Ilievski🇺🇸Columbia University
- Angela M. Lomax-Luu🇺🇸Columbia University
- Faruque Parvez🇺🇸Columbia University
- Hasan Shahriar🇺🇸Columbia University
- Mohammad Nasir Uddin🇺🇸Columbia University
- Tariqul Islam🇺🇸Columbia University
- Joseph H. Graziano🇺🇸Columbia University
- Mary V. Gamble🇺🇸Columbia University
Resumen
El texto original del estudio, en el idioma en que se publicó.
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) 400μg FA/d (400FA; n=153), c) 800μg FA/d (800FA; n=151), d) 3g creatine/d (creatine; n=101), or e) 3g creatine+400μg 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±1.89μg/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.
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