Arsenic Metabolites Measured in Urine
Conditions
Keywords
arsenic, Bangladesh, choline, betaine, methylation
Brief summary
Roughly 140 million people worldwide are chronically exposed to As-contaminated drinking water at concentrations exceeding the World Health Organization (WHO) standard of 10 µg/L. Arsenic is a class I carcinogen known to cause several types of cancer and ischemic heart disease. Metabolism of inorganic As (InAs), which facilitates urinary As excretion, relies on one-carbon metabolism and involves two methylation steps; both utilize S-adenosylmethionine (SAM) as the methyl donor. SAM biosynthesis relies on B vitamins including folate and B12 for the recruitment and transfer of methyl groups, but other nutrients, including choline and betaine, also contribute to the methyl pool. Our recent findings from a cross-sectional study of Bangladeshi adults exposed to a wide range of As concentrations in drinking water show that plasma choline and betaine concentrations are positively associated with As methylation. These findings suggest that choline and/or betaine may play an important role in As methylation and elimination and that simple interventions may have therapeutic potential for the many populations at risk for As-induced health effects. The investigators aim to recruit and follow 60 participants for this pilot study which will allow us to 1) assess the acceptance of choline and betaine supplements, 2) monitor participants for any potential side effects, 3) identify any difficulties that might be encountered in daily follow-up, and 4) generate preliminary data regarding the effects of choline and/or betaine supplementation on arsenic methylation.
Interventions
Sponsors
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age 20-65 * Absence of all
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Urinary % Monomethyl Arsenic | From baseline to 8 weeks after the start of the intervention (week 8 - baseline) |
| Change in Urinary % Inorganic Arsenic | From baseline to 8 weeks after the start of the intervention (week 8 - baseline) |
| Change in Urinary % Dimethyl Arsenic | From baseline to 8 weeks after the start of the intervention (week 8 - baseline) |
Countries
Bangladesh
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo tablets
Placebo | 15 |
| Choline Bitartrate Choline bitartrate 700 mg by mouth daily
Choline bitartrate | 15 |
| Betaine Betaine 1000 mg by mouth daily
Betaine | 15 |
| Choline Bitartrate + Betaine Choline bitartrate 700 mg + Betaine 1000 mg daily
Choline bitartrate + Betaine | 15 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Choline Bitartrate + Betaine | Betaine | Placebo | Choline Bitartrate |
|---|---|---|---|---|---|
| Age, Customized | 31.0 years | 32.0 years | 29.0 years | 30.0 years | 34.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 60 Participants | 15 Participants | 15 Participants | 15 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 60 Participants | 15 Participants | 15 Participants | 15 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Bangladesh | 60 participants | 15 participants | 15 participants | 15 participants | 15 participants |
| Sex: Female, Male Female | 30 Participants | 7 Participants | 7 Participants | 8 Participants | 8 Participants |
| Sex: Female, Male Male | 30 Participants | 8 Participants | 8 Participants | 7 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 15 | 5 / 15 | 2 / 15 | 2 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Change in Urinary % Dimethyl Arsenic
Time frame: From baseline to 8 weeks after the start of the intervention (week 8 - baseline)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change in Urinary % Dimethyl Arsenic | -5.8 percentage of total urinary arsenic |
| Choline Bitartrate | Change in Urinary % Dimethyl Arsenic | 0.65 percentage of total urinary arsenic |
| Betaine | Change in Urinary % Dimethyl Arsenic | -0.87 percentage of total urinary arsenic |
| Choline Bitartrate + Betaine | Change in Urinary % Dimethyl Arsenic | 5.45 percentage of total urinary arsenic |
Primary
Change in Urinary % Inorganic Arsenic
Time frame: From baseline to 8 weeks after the start of the intervention (week 8 - baseline)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change in Urinary % Inorganic Arsenic | 3.0 percentage of total urinary arsenic |
| Choline Bitartrate | Change in Urinary % Inorganic Arsenic | -0.87 percentage of total urinary arsenic |
| Betaine | Change in Urinary % Inorganic Arsenic | -1.25 percentage of total urinary arsenic |
| Choline Bitartrate + Betaine | Change in Urinary % Inorganic Arsenic | -1.7 percentage of total urinary arsenic |
Primary
Change in Urinary % Monomethyl Arsenic
Time frame: From baseline to 8 weeks after the start of the intervention (week 8 - baseline)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change in Urinary % Monomethyl Arsenic | 2.4 percentage of total urinary arsenic |
| Choline Bitartrate | Change in Urinary % Monomethyl Arsenic | 0.24 percentage of total urinary arsenic |
| Betaine | Change in Urinary % Monomethyl Arsenic | -0.06 percentage of total urinary arsenic |
| Choline Bitartrate + Betaine | Change in Urinary % Monomethyl Arsenic | -3.2 percentage of total urinary arsenic |