Superfund Research Program
Nutritional Influences on Blood Arsenic, Arsenic Methylation and Cognitive Function in Children
Project Leader: Mary V. Gamble
Co-Investigators: Joseph H. Graziano, Ana Navas-Acien
Grant Number: P42ES010349
Funding Period: 2006-2021
Project Summary (2017-2021)
The primary goal of this project within the Columbia Superfund Research Program (CU SRP) Center is to conduct a randomized controlled trial (RCT) to evaluate whether folate and B12 supplementation for 8- to 10-year-old children can increase arsenic (As) methylation and lower blood As concentrations.
Ingested inorganic As (InAs) undergoes hepatic methylation to generate mono- (MMA) and di-methyl (DMA) arsenicals using s-adenosylmethionine (SAM) as the methyl donor. This important process facilitates renal As elimination. Methyl groups derived from folate and B12 are essential for the synthesis of SAM through one-carbon metabolism (OCM). Studies in adults from these researchers have determined that folate supplementation increases As methylation and significantly lowers total blood As, particularly blood MMA. However, one cannot assume that folate supplementation would be comparably effective in children because OCM is considerably up-regulated during periods of rapid growth needed to meet the demands for nucleotide and protein biosynthesis, potentially at the expense of methylation reactions.
Aim 1 focuses on whether folate and B12 supplementation can increase As methylation and lower blood As in children. Results over the past 15 years from this group of researchers have documented significant associations between children's exposure to As and poor neurodevelopment. In a follow-up study of 10-year-old children in Bangladesh, reductions in As exposure over time were associated with significant improvement in tests of working memory. Some nutritional deficiencies have well-documented effects on cognitive function in children. However, the influence of folate and B12 deficiency – nutrients known to be required for proper neural development, neurotransmitter synthesis and myelination (in addition to As methylation) – on children's cognitive function have received relatively little attention. There is a high prevalence of folate and B12 deficiencies among young children in Bangladesh. Nutritional deficiencies and As exposure may influence overlapping cognitive outcomes, and may exacerbate As-induced decrements in cognitive function.
In their preliminary study in children, the researchers found that B12 deficiency was associated with lower scores on tests of intelligence in boys, and that folate deficiency was associated with decreased arsenic methylation in both boys and girls. In Aim 2 for this study, the researchers are testing the hypothesis that folate with B12 supplementation for 3 months lowers blood As and blood MMA as compared to placebo. In Aim 3, researchers are evaluating other OCM-related nutritional parameters and their relationship to As methylation in young Native Americans using data from the Strong Heart Family Study. Positive findings of these studies could have profound implications for the health and productivity of many As-exposed populations.