Folic acid supplementation enhances arsenic methylation: results from a folic acid and creatine supplementation randomized controlled trial in Bangladesh.
What this study found
Folic acid supplementation improved arsenic methylation, lowering urinary inorganic arsenic and monomethylarsonic acid and increasing dimethylarsinic acid, with the 800 μg/day dose generally producing a larger effect than 400 μg/day. At weeks 6 and 12, folic acid groups had significantly lower %InAs and %MMAs and higher %DMAs versus placebo; the 800 μg group showed a larger reduction in %MMAs than the 400 μg group at weeks 6 and 12 (P = 0.034). Creatine had a smaller effect, mainly lowering %MMAs without changing %InAs or %DMAs. After folic acid was stopped, metabolite proportions tended to…
- Study & population
- Randomized controlled trial in arsenic-exposed Bangladeshi adults from Araihazar, recruited from the HEALS cohort.
- Intervention
- Adults were assigned to oral daily supplements for 12 weeks: folic acid 400 μg/day, folic acid 800 μg/day, creatine 3 g/day, or creatine 3 g/day plus folic acid 400 μg/day, all given as pills.
- Key limitation
- The trial was relatively short and relied on biomarker outcomes rather than clinical endpoints.
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Open PDFOriginal 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.