Mitigation Efforts in Arsenic Exposure With Folic Acid Supplementation

Mitigation Efforts in Arsenic Exposure With Folic Acid Supplementation: Reducing Toxicity and Exploring the Impact on Lung Health

The purpose of this study is to evaluate the effects on folic acid supplementation in a population living in an environment with chronic arsenic exposure in Birmingham, Alabama.

Study Overview

• Status: Enrolling by invitation
• Conditions: Arsenic and/or Arsenic Compound Adverse Reaction
• Intervention / Treatment: Other: Placebo; Dietary supplement: Folic Acid

Detailed Description

Folic acid supplementation effects urinary arsenic excretion. In this project investigators propose to investigate if oral folic acid dietary supplementation can increase urinary arsenic metabolite excretion

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • UAB Lung Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• ≥18 years of age
• Resident of the superfund site
• Clinically stable with no significant changes in general health status in the past 4 weeks prior to screening as assessed by the investigator
• Provide written informed consent

Exclusion Criteria:

• Pregnancy
• Ongoing folic acid nutritional supplementation
• Methotrexate use
• Megaloblastic anemia
• Alcoholic liver disease
• Malabsorptive syndromes - celiac disease, inflammatory bowel disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo daily 12 weeks	Other: Placebo; Placebo group to assess arsenic metabolite excretion
Experimental: Folic Acid; Folic acid 800 ug/day 12 weeks	Dietary supplement: Folic Acid; Folic acid supplementation to assess for increased arsenic metabolite excretion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of urine and blood arsenic metabolites	Inorganic As (InAs) within humans undergoes a stepwise biotransformation reaction in which it is methylated to monomethyl-arsonic acid (MMAsIII), and dimethylarsinic acid (DMAsV) facilitating urinary excretion. This occurs via arsenic methyltransferase (AS3MT) using a methyl donor S-adenosylmethionine (SAM). In this pathway the one-carbon unit carried by 5-methyl-tetrahydrofolate (5-MTHF) is transferred to homocysteine to form methionine, which is activated to SAM. Complete methylation to DMAsV is critical as higher proportion of MMAs(III+V) are associated with skin lesions, peripheral vascular disease, atherosclerosis, and cancers. We will measure levels of InAs, total DMA and MMA in the urine and blood of the study subjects at baseline and 12 weeks. Outcomes will be reported in percentage (%) of InAs, DMA and MMA in blood and urine.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory Symptom Questionnaire	The Respiratory Symptom Questionnaire (RSQ) is an instrument that assesses the frequency of respiratory symptoms and their impact on patients' activity over the previous four weeks, without requiring a specific diagnostic label of asthma or chronic obstructive pulmonary disease (COPD). The four questions assess the frequency of respiratory symptoms (shortness of breath, wheezing, coughing, and/or chest tightness) during the day and, in response to these respiratory symptoms, frequency of rescue inhaler use, activity limitations and frequency of night-time awakening. We will administer the RSQ to participants at the baseline screening. Maximum value 16, minimum value 4, higher scores represent increased symptom burden.	12 weeks
Pooled Cohort Probability Score	The pooled cohort probability score has been used to detect subclinical airway obstruction. Age, sex, race and/or ethnicity, body mass index, smoking status, and smoking pack-years will be obtained and the score will be computed at baseline.	12 weeks

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: National Institute of Environmental Health Sciences (NIEHS); P42ES027723
• Investigators: Principal Investigator: Kevin G Dsouza, MD, University of Alabama at Birmingham

Publications and helpful links

General Publications

• Bozack AK, Hall MN, Liu X, Ilievski V, Lomax-Luu AM, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Graziano JH, Gamble MV. Folic acid supplementation enhances arsenic methylation: results from a folic acid and creatine supplementation randomized controlled trial in Bangladesh. Am J Clin Nutr. 2019 Feb 1;109(2):380-391. doi: 10.1093/ajcn/nqy148.

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 10, 2022
• First Submitted That Met QC Criteria: December 12, 2022
• First Posted (Actual): December 19, 2022

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pterins; Pteridines; Folic Acid
• Other Study ID Numbers: 300010144; P42ES027723 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No