Betaine and choline status modify the effects of folic acid and creatine supplementation on arsenic methylation in a randomized controlled trial of Bangladeshi adults

Purpose Methylation of ingested inorganic arsenic (InAs) to monomethyl- (MMAs) and dimethyl-arsenical species (DMAs) facilitates urinary arsenic elimination. Folate and creatine supplementation influenced arsenic methylation in a randomized controlled trial. Here, we examine if baseline status of one-carbon metabolism nutrients (folate, choline, betaine, and vitamin B-12) modified the effects of FA and creatine supplementation on changes in homocysteine, guanidinoacetate (GAA), total blood arsenic, and urinary arsenic metabolite proportions and indices. Methods Study participants (N = 622) received 400 or 800 mu g FA, 3 g creatine, 400 mu g FA + 3 g creatine, or placebo daily for 12 weeks. Results Relative to placebo, FA supplementation was associated with greater mean increases in %DMAs among participants with betaine concentrations below the median than those with levels above the median (FDR < 0.05). 400 mu g FA/day was associated with a greater decrease in homocysteine among participants with plasma folate concentrations below, compared with those above, the median (FDR < 0.03). Creatine treatment was associated with a significant decrease in %MMAs among participants with choline concentrations below the median (P = 0.04), but not among participants above the median (P = 0.94); this effect did not significantly differ between strata (P = 0.10). Conclusions Effects of FA and creatine supplementation on arsenic methylation capacity were greater among individuals with low betaine and choline status, respectively. The efficacy of FA and creatine interventions to facilitate arsenic methylation may be modified by choline and betaine nutritional status.