Nutrients in one-carbon metabolism and urinary arsenic methylation in the National Health and Nutrition Examination Survey (NHANES) 2003–2004

Abstract

Exposure to inorganic arsenic (inAs), a potent toxicant, occurs primarily through ingestion of food and water. The efficiency with which it is methylated to mono and dimethyl arsenicals (MMA and DMA) affects toxicity. Folate, vitamins B12 and B6 are required for 1C metabolism, and studies have found that higher levels of these nutrients increase methylation capacity and are associated with protection against adverse health effects from inAs, especially in undernourished populations. Our aim was to determine whether 1C-related nutrients are associated with greater inAs methylation capacity in a general population sample with overall adequate nutrition and low levels of As exposure. Univariate and multivariable regression models were used to evaluate the relationship of dietary and blood nutrients to urinary As methylation in the National Health and Nutrition Examination Survey (NHANES) 2003-2004. Outcome variables were the percent of the sum of inAs and methylated As species (inAs+MMA+DMA) excreted as inAs, MMA, and DMA, and the ratio of MMA:DMA. In univariate models, dietary folate, vitamin B6 and protein intake were associated with lower urinary inAs% and greater DMA% in adults (≥18years), with similar trends in children (6-18). In adjusted models, vitamin B6 intake (p=0.011) and RBC folate (p=0.036) were associated with lower inAs%, while dietary vitamin B12 was associated with higher inAs% (p=0.002) and lower DMA% (p=0.030). Total plasma homocysteine was associated with higher MMA% (p=0.004) and lower DMA% (p=0.003), but not with inAs%; other blood nutrients showed no association with urinary As. Although effect size is small, these findings suggest that 1C nutrients can influence inAs methylation and potentially play an indirect role in reducing toxicity in a general population sample.

Association of One-Carbon Metabolism-Related Vitamins (Folate, B6, B12), Homocysteine and Methionine With the Risk of Lung Cancer: Systematic Review and Meta-Analysis

“…A growing body of evidence shows that DNA methylation plays an important role in the progression of cancers ( 3 ). DNA methylation requires a methyl donor, which is mainly provided by one-carbon metabolism (OCM) ( 4 , 5 ). S-adenosylmethionine (SAM), the activated form of methionine, serves as the most important methyl donor.…”

Effect of a Supplementation with Two Quelites on Urinary Excretion of Arsenic in Adolescents Exposed to Water Contaminated with the Metalloid in a Community in the State of Guanajuato, Mexico

“…On the other hand, As can also have different excretion patterns in participants of the same group (intra-individual variability; inter-individual variability) [52] or between groups [28,51]. However, the literature reports that many factors influence arsenic metabolism and condition its efficiency, including genetic factors (example: polymorphisms of the arsenite methyltransferase), metabolic capacity, sex, hormonal mechanisms, nutritional status, and diet [28,48,52,53].…”

“…However, nowadays the importance of consuming these potential sources of phytochemicals such as quelites has been forgotten, which could be used as alternative therapies to reduce the effects of various pathophysiological conditions, including As toxicity [21]. Some studies on populations exposed to As have reported that the consumption of natural supplements or foods rich in bioactive compounds improve the processes of methylation and increase the levels of excretion of As, promoting an efficient recovery process [28,42,53,56]. On the other hand, nutritional deficiencies due to low consumption of micronutrients contribute to increasing the risk of arsenic-induced skin lesions [57].…”

“…On the other hand, other studies report that vitamin C, methionine, and cysteine participate in the processes of As detoxification, promoting chelation and facilitating its removal from the body [14,42]. Finally, according to Kurzius-Spencer et al [53], some amino acids are associated with the 1-carbon pathway such as methionine, cysteine, serine, and glycine, promoting the As methylation process. Other mechanisms have been reported to explain the beneficial effects of these nutrients and the exposure of As.…”

Gene-environment interaction and maternal arsenic methylation efficiency during pregnancy

“…Other than As3MT , SNPs in N6AMT1, GSTO , and GLRX , as well as some genes that may not be closely involved in the arsenic methylation process, are associated with the concentrations or percentages of urinary arsenic metabolites ( Antonelli et al, 2014 ; Beebe-Dimmer et al, 2012 ; Gao et al, 2015 ; Harari et al, 2013 ). For example, one-carbon metabolism (OCM) is a biochemical pathway that is able to provide methyl groups for arsenic methylation, and related nutritional status is reported associated with arsenic methylation efficiency in pregnant and non-pregnant cohorts ( Bozack et al, 2018 ; Kurzius-Spencer et al, 2017 ; Laine et al, 2018 ). Methylenetetrahydrofolate reductase (encoded by MTHFR ) is an important enzyme involved in OCM, and plays a role in the supplement of SAM in arsenic metabolism ( Chung et al, 2010 ; Wlodarczyk et al, 2012 ).…”