Biological Sciences Division
Published July 16, 2025 | Version v1
Journal article Metadata-only

Metabolic Signature of Arsenic Exposure and Metabolism: The Folic Acid and Creatine Trial

Creators

  • 1. Columbia University
  • 2. Icahn School of Medicine at Mount Sinai
  • 3. University of Chicago
  • 4. Baylor Scott and White Research Institute
  • 5. Emory University

Description

Arsenic exposure remains a leading public health concern. Folic acid (FA) supplementation enhances one-carbon metabolism (OCM), thus promoting arsenic methylation and facilitating urinary arsenic elimination. Here, we investigate the metabolic profiles linked to arsenic exposure and metabolism based on a FA clinical trial. Arsenic exposure was assessed by the concentrations of blood arsenic (bAs) species: arsenite [InAsIII], arsenate [InAsV], monomethyl- [MMA], and dimethyl- [DMA] arsenicals. Arsenic metabolism was assessed by the relative distribution (%) of these arsenicals in urine. Nontargeted metabolomic profiling was analyzed by LC-HRMS. OCM-related metabolites were analyzed by HPLC/MS/MS. Metabolomic profiling identified 8 unique metabolites and 812 metabolomic features (FDR < 0.05) associated with bAs (predominantly AsV), and 66 metabolites and 285 metabolomic features with %uAs (predominantly %uInAs). Metabolic pathways enriched for bAs and %uAs were similar, highlighting phenylalanine, tyrosine, and tryptophan biosynthesis. A FA-induced %uInAs change was associated with four metabolites, three of which share links to acetyl-CoA metabolism. Of 11 measured OCM metabolites, cystathionine was positively associated with all bAs species. Methionine, S-adenosylmethionine, S-adenosylhomocysteine, cysteine, choline, betaine, and dimethylglycine were associated with increased As methylation profiles in urine (FDR < 0.05). Collectively, these findings may aid in the discovery of mechanisms underlying arsenic-induced health outcomes and potential targeted interventions. This trial was registered with clinicaltrials.gov: NCT01050556

Additional details

Identifiers

DOI
10.1021/acs.est.5c01597
Other
oai:uchicago.tind.io:16210

Funding

National Institutes of Health
P30 ES009089
National Institutes of Health
P42ES033719
National Institutes of Health
P42ES10349
National Institutes of Health
R01CA133595
National Institutes of Health
R01DK123285
National Institutes of Health
R01ES030945

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Human Genetics, Public Health Sciences
Center(s) or Institute(s)
Comprehensive Cancer Center