Abstract
Arsenic is a prevalent environmental contaminant, and its folate-dependent methylation is important for detoxification in the body. In this study, we investigated the association between serum folate levels and methylation using data from the US National Health and Nutrition Examination Survey (NHANES) (2003–2012) (N = 11,016). Multivariate linear regression and penalized spline regression models were used to examine the association and possible upper limit of folate level regarding its impact on methylation in children (≤18 years) and adults (>18 years), respectively. Serum folate levels, methylation metabolites including urinary monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)), and demographic variables were extracted from NHANES. Results showed that urinary percentage of DMA(V) (%DMA(V)) was positively associated with log(serum folate levels) after adjustment in children (β = 1.93, p < 0.01); urinary percentage of MMA(V) (%MMA(V)) was positively associated with log (serum folate levels) after adjustment in adults (β = 0.40, p < 0.01). No upper limit of folate level regarding its impact on arsenic methylation was identified. More than 50% of Non-Hispanic black and smokers with high total urinary arsenic levels had low serum folate levels. Our results indicate that folate promotes arsenic methylation, but the patterns are different in children versus in adults. Future interventions may be needed for the population exposed to high level of arsenic but with low serum folate to protect against the potential adverse health effects of arsenic.
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References
Winski SL, Carter DE. Interactions of rat red blood cell sulfhydryls with arsenate and arsenite. J Toxicol Environ Health. 1995;46:379–97.
Jomova K, Valko M. Advances in metal-induced oxidative stress and human disease. Toxicology . 2011;283:65–87.
Hughes MF, Beck BD, Chen Y, Lewis AS, Thomas DJ. Arsenic exposure and toxicology: a historical perspective. Toxicol Sci. 2011;123:305–32.
Yu H, Liu S, Li M, Wu B. Influence of diet, vitamin, tea, trace elements and exogenous antioxidants on arsenic metabolism and toxicity. Environ Geochem Health. 2016;38:339–51. Springer Netherlands
Hsueh Y-M, Chen W-J, Lee C-Y, Chien S-N, Shiue H-S, Huang S-R, et al. Association of arsenic methylation capacity with developmental delays and health status in children: a prospective case–control trial. Nat Publ Gr. 2016;1–9. Doi:10.1038/srep37287.
Vahter M, Concha G. Role of metabolism in arsenic toxicity. Pharmacol Toxicol. 2001;89:1–5.
Tseng CH. A review on environmental factors regulating arsenic methylation in humans. Toxicol Appl Pharmacol. 2009;235:338–50.
Shen H, Niu Q, Xu M, Rui D, Xu S, Feng G, et al. Factors affecting arsenic methylation in arsenic-exposed humans: a systematic review and meta-analysis. Int J Environ Res Public Health. 2016;13:205.
López-Carrillo L, Gamboa-Loira B, Becerra W, Hernández-Alcaraz C, Ulises Hernández-Ramírez R, Gandolfi AJ, et al. Dietary micronutrient intake and its relationship with arsenic metabolism in Mexican women. Environ Res. 2016;151:445–50.
Chowdhury UK, Rahman MM, Sengupta MK, Lodh D, Chanda CR, Roy S, et al. Pattern of excretion of arsenic compounds arsenite, arsenate, MMA(V), DMA(V) in urine of children compared to adults from an arsenic exposed area in Bangladesh. J Environ Sci Heal Part A. 2003;38:87–113.
Hall M, Gamble M, Slavkovich V, Liu X, Levy D, Cheng Z, et al. Determinants of arsenic metabolism: blood arsenic metabolites, plasma folate, cobalamin, and homocysteine concentrations in maternal-newborn pairs. Environ Health Perspect. 2007;115:1503–9.
Gamble MV, Liu X, Ahsan H, Pilsner JR, Illievski V, Slavkovich V, et al. Folate, homocysteine, and arsenic metabolism in arsenic-exposed individuals in Bangladesh. Environ Health Perspect. 2005;113:1683–88.
Heck JE, Gamble MV, Chen Y, Graziano JH, Slavkovich V, Parvez F, et al. Consumption of folate-related nutrients and metabolism of arsenic in Bangladesh. Am J Clin Nutr. 2007;85:1367–74.
Gamble MV, Liu X, Slavkovich V, Pilsner JR, Ilievski V, Factor-Litvak P, et al. Folic acid supplementation lowers blood arsenic. Am J Clin Nutr. 2007;86:1202–9.
Löveborn HS, Kippler M, Lu Y, Ahmed S, Kuehnelt D, Raqib R, et al. Arsenic metabolism in children differs from that in adults. Toxicol Sci. 2016;152:29–39.
Cardenas A, Smit E, Bethel JW, Houseman EA, Kile ML. Arsenic exposure and the seroprevalence of total hepatitis A antibodies in the US population: NHANES, 2003-2012. Epidemiol Infect. 2016;144:1–11.
Fazili Z, Pfeiffer CM, Zhang M. Comparison of serum folate species analyzed by LC-MS/MS with total folate measured by microbiologic assay and Bio-Rad radioassay. Clin Chem. 2007;53:781–84.
Borrud L, Chiappa MM, Burt VL, Gahche J, Zipf G, Johnson CL, et al. National Health and Nutrition Examination Survey: national youth fitness survey plan, operations, and analysis, 2012. Vital Heal Stat—Ser 2 Data Eval Methods Res. 2014;162:1–24.
Benowitz NL, Bernert JT, Caraballo RS, Holiday DB, Wang J. Optimal serum cotinine levels for distinguishing cigarette smokers and nonsmokers within different racial/ethnic groups in the United States between 1999 and 2004. Am J Epidemiol. 2009;169:236–48.
Kile ML, Ronnenberg AG. Can folate intake reduce arsenic toxicity? Nutr Rev. 2008;66:349–53.
Hall MN, Liu X, Slavkovich V, Ilievski V, Pilsner JR, Alam S, et al. Folate, cobalamin, cysteine, homocysteine, and arsenic metabolism among children in Bangladesh. Environ Health Perspect. 2009;117:825–31.
Meza MM, Yu L, Rodriguez YY, Guild M, Thompson D, Gandolfi AJ, et al. Developmentally restricted genetic determinants of human arsenic metabolism: association between urinary methylated arsenic and CYT19 polymorphisms in children. Environ Health Perspect. 2005;113:775–81.
Pfeiffer CM, Caudill SP, Gunter EW, Osterloh J, Sampson EJ. Biochemical indicators of B vitamin status in the US population after folic acid fortification: results from the National Health and Nutrition Examination Survey 1999-2000. Am J Clin Nutr. 2005;82:442–50.
Dinse GE, Jusko TA, Ho LA, Annam K, Graubard BI, Hertz-Picciotto I, et al. Accommodating measurements below a limit of detection: A novel application of cox regression. Am J Epidemiol. 2014;179:1018–24.
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Zhang, X., Xu, X., Zhong, Y. et al. Serum folate levels and urinary arsenic methylation profiles in the US population: NHANES, 2003–2012. J Expo Sci Environ Epidemiol 29, 323–334 (2019). https://doi.org/10.1038/s41370-018-0021-5
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DOI: https://doi.org/10.1038/s41370-018-0021-5