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Folic acid supplementation enhances arsenic methylation: results from a folic acid and creatine supplementation randomized controlled trial in Bangladesh.
Bozack, AK, Hall, MN, Liu, X, Ilievski, V, Lomax-Luu, AM, Parvez, F, Siddique, AB, Shahriar, H, Uddin, MN, Islam, T, et al
The American journal of clinical nutrition. 2019;(2):380-391
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Abstract
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 μg per day), 3 g creatine per day, 400 μg 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 µg FA than in the 400 µg FA group (P = 0.034). There were no differences in treatment effects between the 400 µg 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.
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Arsenic in seafood is associated with increased thyroid-stimulating hormone (TSH) in healthy volunteers - A randomized controlled trial.
Molin, M, Ulven, SM, Dahl, L, Lundebye, AK, Holck, M, Alexander, J, Meltzer, HM, Ydersbond, TA
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2017;:1-7
Abstract
BACKGROUND Exposure to exogenous elements like arsenic (As) may influence thyroid enzymes, thyroid-stimulating hormone (TSH), and the two principal thyroid hormones, free thyroxine (FT4) and free triiodothyronine (FT3), but little is known about how this is related to organic arsenicals, the main form in seafood. AIM: To investigate whether a high intake of dietary arsenic from seafood can impact thyroid function and thyroid hormones by examining possible associations with changes in TSH, FT4, FT3 and the FT4:FT3-ratio in plasma. METHODS Thirty-eight healthy subjects were randomized into four groups. During a 14-day semi-controlled dietary study, the subjects ingested daily portions of either 150g cod, salmon, blue mussels or potato (control). Plasma concentrations of total As, FT3, FT4, TSH and selenium (Se), and urinary concentrations of iodine were monitored. RESULTS Plasma concentrations of TSH increased significantly in all seafood groups. The change in plasma As, with different coefficients for each seafood group, was the dominant factor in the optimal multiple regression model for change in TSH (R2=0.47). Plasma Se and iodine were negative and positive factors, respectively. There were also indications of changes in FT4, FT3 and the FT4:FT3 ratio consistent with a net inhibiting effect of As on FT4 to FT3 conversion. CONCLUSION Ingestion of seafood rich in various organic As species was strongly associated with an increase of the TSH concentrations in plasma. Change in TSH was positively associated with total plasma As, but varied with the type of seafood ingested. These findings indicate that organic dietary As, apparently depending on chemical form, may influence thyroid hormones and function.
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Sex-Specific Associations between One-Carbon Metabolism Indices and Posttranslational Histone Modifications in Arsenic-Exposed Bangladeshi Adults.
Howe, CG, Liu, X, Hall, MN, Ilievski, V, Caudill, MA, Malysheva, O, Lomax-Luu, AM, Parvez, F, Siddique, AB, Shahriar, H, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2017;(2):261-269
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Abstract
BACKGROUND Posttranslational histone modifications (PTHMs) are altered by arsenic, an environmental carcinogen. PTHMs are also influenced by nutritional methyl donors involved in one-carbon metabolism (OCM), which may protect against epigenetic dysregulation. METHODS We measured global levels of three PTHMs, which are dysregulated in cancers (H3K36me2, H3K36me3, H3K79me2), in peripheral blood mononuclear cells (PBMC) from 324 participants enrolled in the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults. Sex-specific associations between several blood OCM indices (folate, vitamin B12, choline, betaine, homocysteine) and PTHMs were examined at baseline using regression models, adjusted for multiple tests by controlling for the false discovery rate (PFDR). We also evaluated the effects of folic acid supplementation (400 μg/d for 12 weeks), compared with placebo, on PTHMs. RESULTS Associations between choline and H3K36me2 and between vitamin B12 and H3K79me2 differed significantly by sex (Pdiff < 0.01 and <0.05, respectively). Among men, plasma choline was positively associated with H3K36me2 (PFDR < 0.05), and among women, plasma vitamin B12 was positively associated with H3K79me2 (PFDR < 0.01). Folic acid supplementation did not alter any of the PTHMs examined (PFDR = 0.80). CONCLUSIONS OCM indices may influence PTHMs in a sex-dependent manner, and folic acid supplementation, at this dose and duration, does not alter PTHMs in PBMCs. IMPACT This is the first study to examine the influences of OCM indices on PTHMs in a population that may have increased susceptibility to cancer development due to widespread exposure to arsenic-contaminated drinking water and a high prevalence of hyperhomocysteinemia. Cancer Epidemiol Biomarkers Prev; 26(2); 261-9. ©2016 AACR.
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Supplementation with Folic Acid, but Not Creatine, Increases Plasma Betaine, Decreases Plasma Dimethylglycine, and Prevents a Decrease in Plasma Choline in Arsenic-Exposed Bangladeshi Adults.
Hall, MN, Howe, CG, Liu, X, Caudill, MA, Malysheva, O, Ilievski, V, Lomax-Luu, AM, Parvez, F, Siddique, AB, Shahriar, H, et al
The Journal of nutrition. 2016;(5):1062-7
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Abstract
BACKGROUND Folic acid (FA) supplementation facilitates urinary excretion of arsenic, a human carcinogen. A better understanding of interactions between one-carbon metabolism intermediates may improve the ability to design nutrition interventions that further facilitate arsenic excretion. OBJECTIVE The objective was to determine if FA and/or creatine supplementation increase choline and betaine and decrease dimethylglycine (DMG). METHODS We conducted a secondary analysis of the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults (n = 605, aged 24-55 y, 50.3% male) who received arsenic-removal water filters. We examined treatment effects of FA and/or creatine supplementation on plasma choline, betaine, and DMG concentrations, measured by LC-tandem mass spectrometry at baseline and at week 12. Group comparisons were between 1) 400 and 800 μg FA/d (FA400 and FA800, respectively) compared with placebo, 2) creatine (3 g/d) compared with placebo, and 3) creatine plus FA400 compared with FA400. RESULTS Choline decreased in the placebo group (-6.6%; 95% CI: -10.2%, -2.9%) but did not change in the FA groups (FA400: 2.5%; 95% CI: -0.9%, 6.1%; FA800: 1.4%; 95% CI: -2.5%, 5.5%; P < 0.05). Betaine did not change in the placebo group (-3.5%; 95% CI: -9.3%, 2.6%) but increased in the FA groups (FA400: 14.1%; 95% CI: 9.4%, 19.0%; FA800: 13.0%; 95% CI: 7.2%, 19.1%; P < 0.01). The decrease in DMG was greater in the FA groups (FA400: -26.7%; 95% CI: -30.9%, -22.2%; FA800: -27.8%; 95% CI: -31.8%, -23.4%) than in the placebo group (-12.3%; 95% CI: -18.1%, -6.2%; P < 0.01). The percentage change in choline, betaine, and DMG did not differ between creatine treatment arms and their respective reference groups. CONCLUSION Supplementation for 12 wk with FA, but not creatine, increases plasma betaine, decreases plasma DMG, and prevents a decrease in plasma choline in arsenic-exposed Bangladeshi adults. This trial was registered at clinicaltrials.gov as NCT01050556.
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Smoking and chronic rhinitis: effects of nasal irrigations with sulfurous-arsenical-ferruginous thermal water: A prospective, randomized, double-blind study.
Ottaviano, G, Marioni, G, Giacomelli, L, La Torre, FB, Staffieri, C, Marchese-Ragona, R, Staffieri, A
American journal of otolaryngology. 2012;(6):657-62
Abstract
PURPOSE Smoking is a self-destructive behavior that is known to induce remodeling of the lower airways, leading to squamous metaplasia, but little is known about its effects on the nose and paranasal sinuses. Nasal irrigations are often mentioned as measures for treating sinonasal inflammations. The purpose of our study was to compare the effects of nasal irrigations with sulfurous-arsenical-ferruginous thermal water or isotonic sodium chloride solution in smokers with nonallergic chronic rhinosinusitis, based on clinical and olfactory evidence. MATERIALS AND METHODS The present study was a prospective, randomized, double-blind study performed in a tertiary academic referral center. Seventy smokers with nonallergic chronic rhinitis were enrolled. Nasal endoscopy, rhinomanometry, nasal cytology, and odor threshold measurements were performed in subjects randomized to daily nasal irrigations with either thermal water or isotonic sodium chloride solution for 1 month. RESULTS Immediately after the treatment, the thermal water irrigations revealed a positive pharmacologic action, judging from a tendency toward lower nasal resistances (P = .07) and larger numbers of ciliated cells in the patients treated (P = .003). Endoscopic findings in the thermal water group were still better than in the control group a further 2 months later (P = .03). CONCLUSIONS Our results indicate that nasal irrigations with thermal water had a good effect on endoscopic objective signs, nasal resistances, and epithelial trophism.