High Blood Arsenic Due to Chronic Arsenic ExposurePhase 4FACTANCT01050556
Folic Acid and Creatine as Therapeutic Approaches for Lowering Blood Arsenic
A Phase 4 study testing folic acid, creatine and creatine + folic acid in people with High Blood Arsenic Due to Chronic Arsenic Exposure, run by Columbia University at 1 site in Bangladesh.
Trial summary
The purpose of this study is to determine whether folic acid, alone or together with creatine supplementation, can lower blood arsenic concentrations and improve the ability to detoxify arsenic. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- High Blood Arsenic Due to Chronic Arsenic Exposure
- What is being tested?
- folic acid, creatine and creatine + folic acid
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 600 participants
- Where
- 1 siteBangladesh
- Study dates
- Sep 2010to Jun 2011
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Currently exposed to arsenic via contaminated drinking water
- Well water arsenic concentration > 10 ug/L
- Between the ages of 20 and 65
Who cannot join
- Women who are currently pregnant or plan to become pregnant within the next 6 months
- Currently taking nutritional supplements
- Known renal disease
- Participation in any other clinical trial
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to determine whether folic acid, alone or together with creatine supplementation, can lower blood arsenic concentrations and improve the ability to detoxify arsenic.
Read the detailed description
Approximately 140 million people in over 70 countries are chronically exposed to arsenic (As)-contaminated drinking water at concentrations far exceeding the World Health Organization standard of 10 µg/L. As is a carcinogen known to cause cancers of the skin, bladder, and lung, as well as ischemic heart disease and neurologic impairments. Methylation of ingested inorganic arsenic (InAs) to methylarsonic-(MMA) and dimethylarsinic acids (DMA) relies on folate-dependent one carbon metabolism, utilizing S-adenosylmethionine (SAM) as the methyl donor, and facilitates urinary As elimination. The results from our Nutritional Influences on Arsenic Toxicity (NIAT) study indicate that folate deficiency and hyperhomocysteinemia (HHcys) are associated with a reduced capacity to methylate arsenic and are risk factors for arsenic-induced skin lesions. Furthermore, folic acid (FA) supplementation does indeed facilitate As elimination and significantly lowers blood As concentrations in individuals who are folate deficient. We have also determined that blood As is a good biomarker of As exposure and is directly associated with the risk for As-induced skin lesions. Collectively, the implication of these findings is that FA has enormous therapeutic potential for ameliorating the long-term health consequences of arsenic exposure for the many populations at risk. However, several fundamental questions remain and will be addressed in this study. This trial is designed to determine 1) whether FA supplementation lowers blood As concentrations in the general Bangladeshi population, 2) at what time point a nadir in blood As is achieved, and 3) whether creatine supplementation, alone or in addition to 400 µg/d FA, will spare methyl groups, resulting in lower blood As, lower homocysteine (Hcys) concentrations, and increased methylation of As. The creatine arms are based on multiple studies that show that urinary creatinine concentrations are a very strong predictor of As methylation. The final step in creatine biosynthesis is the methylation of guanidinoacetate to creatine; this process consumes 50-75% of all SAM-derived methyl groups and is also responsible for 50-75% of all Hcys biosynthesis. Thus, this trial will test the hypothesis that creatine supplementation, which shuts down endogenous creatine biosynthesis, will spare methyl groups, lower Hcys, and increase As methylation.
- Being tested
- Placebo, folic acid, creatine, creatine + folic acid
- Keywords
- arsenic, folate, folic acid, creatine, arsenicosis, nutrition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
daily, 24 weeks
folic acidDietary supplement
400 ug/d for 12 or 24 weeks
folic acidDietary supplement
800 µg/d for 12 or 24 weeks
creatineDietary supplement
3 mg/d for 12 weeks
creatine + folic acidDietary supplement
3 mg creatine/d + 400 µg folic acid/d for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo daily Receives: Other: Placebo |
| Folic Acid 400 ug | Experimental | 400 µg folic acid daily Receives: Dietary Supplement: folic acid |
| Folic Acid 800 ug | Experimental | 800 µg folic acid daily Receives: Dietary Supplement: folic acid |
| Creatine | Experimental | creatine daily Receives: Dietary Supplement: creatine |
| Creatine + Folic Acid | Experimental | creatine + folic acid daily Receives: Dietary Supplement: creatine + folic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
blood arsenic concentrations
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2010 (estimated)
- Study startSep 2010
- Primary completionJun 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for High Blood Arsenic Due to Chronic Arsenic ExposureStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 600 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Mary Gamble, Columbia University
- Investigators
- Mary V Gamble, PhD, Principal investigator, Columbia University, Department of Environmental Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01050556
- Sponsor's protocol ID
- AAAC8618
- Other IDs
- R01CA133595
- Acronym
- FACTA
- Status last verified
- Jul 2012
- First submitted
- 13 Jan 2010
- Last updated
- 1 Aug 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Li W, Wu H, Goldsmith J, Glabonjat RA, Ilievski V, Balac O, Slavkovich V, Pinto-Pacheco B, Lin X, Parvez F, Jackson GL, Siddique AB, Uddin MN, Islam T, Martinez-Morata I, Navas-Acien A, Niedzwiecki MM, Kioumourtzoglou MA, Pierce BL, Graziano JH, Bottiglieri T, Walker DI, Gamble MV. Metabolic Signature of Arsenic Exposure and Metabolism: The Folic Acid and Creatine Trial. Environ Sci Technol. 2025 Jul 29;59(29):14905-14916. doi: 10.1021/acs.est.5c01597. Epub 2025 Jul 16.
PubMed 40668877Martinez-Morata I, Wu H, Galvez-Fernandez M, Ilievski V, Bottiglieri T, Niedzwiecki MM, Goldsmith J, Jones DP, Kioumourtzoglou MA, Pierce B, Walker DI, Gamble MV. Metabolomic Effects of Folic Acid Supplementation in Adults: Evidence from the FACT Trial. J Nutr. 2024 Feb;154(2):670-679. doi: 10.1016/j.tjnut.2023.12.010. Epub 2023 Dec 12.
PubMed 38092151Abuawad AK, Bozack AK, Navas-Acien A, Goldsmith J, Liu X, Hall MN, Ilievski V, Lomax-Luu AM, Parvez F, Shahriar H, Uddin MN, Islam T, Graziano JH, Gamble MV. The Folic Acid and Creatine Trial: Treatment Effects of Supplementation on Arsenic Methylation Indices and Metabolite Concentrations in Blood in a Bangladeshi Population. Environ Health Perspect. 2023 Mar;131(3):37015. doi: 10.1289/EHP11270. Epub 2023 Mar 28.
PubMed 36976258Bae S, Kamynina E, Guetterman HM, Farinola AF, Caudill MA, Berry RJ, Cassano PA, Stover PJ. Provision of folic acid for reducing arsenic toxicity in arsenic-exposed children and adults. Cochrane Database Syst Rev. 2021 Oct 18;10(10):CD012649. doi: 10.1002/14651858.CD012649.pub2.
PubMed 34661903Bozack AK, Howe CG, Hall MN, Liu X, Slavkovich V, Ilievski V, Lomax-Luu AM, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Graziano JH, Gamble MV. Betaine and choline status modify the effects of folic acid and creatine supplementation on arsenic methylation in a randomized controlled trial of Bangladeshi adults. Eur J Nutr. 2021 Jun;60(4):1921-1934. doi: 10.1007/s00394-020-02377-z. Epub 2020 Sep 11.
PubMed 32918135Bozack 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.
PubMed 30590411Hall MN, Howe CG, Liu X, Caudill MA, Malysheva O, Ilievski V, Lomax-Luu AM, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Graziano JH, Gamble MV. Supplementation with Folic Acid, but Not Creatine, Increases Plasma Betaine, Decreases Plasma Dimethylglycine, and Prevents a Decrease in Plasma Choline in Arsenic-Exposed Bangladeshi Adults. J Nutr. 2016 May;146(5):1062-7. doi: 10.3945/jn.115.227132. Epub 2016 Apr 6.
PubMed 27052531Peters BA, Hall MN, Liu X, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Ilievski V, Graziano JH, Gamble MV. Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial. J Nutr. 2015 Oct;145(10):2245-52. doi: 10.3945/jn.115.216739. Epub 2015 Aug 26.
PubMed 26311810
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Folic Acid and Creatine as Therapeutic Approaches for Lowering Blood Arsenic
- ClinicalTrials.gov ID
- NCT01050556
- Acronym / sponsor ID
- FACTA / AAAC8618
- Keywords
- arsenic, folate, folic acid, creatine, arsenicosis, nutrition
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 600 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 2010
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 15 Jan 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether folic acid, alone or together with creatine supplementation, can lower blood arsenic concentrations and improve the ability to detoxify arsenic.
Detailed description
Approximately 140 million people in over 70 countries are chronically exposed to arsenic (As)-contaminated drinking water at concentrations far exceeding the World Health Organization standard of 10 µg/L. As is a carcinogen known to cause cancers of the skin, bladder, and lung, as well as ischemic heart disease and neurologic impairments. Methylation of ingested inorganic arsenic (InAs) to methylarsonic-(MMA) and dimethylarsinic acids (DMA) relies on folate-dependent one carbon metabolism, utilizing S-adenosylmethionine (SAM) as the methyl donor, and facilitates urinary As elimination. The results from our Nutritional Influences on Arsenic Toxicity (NIAT) study indicate that folate deficiency and hyperhomocysteinemia (HHcys) are associated with a reduced capacity to methylate arsenic and are risk factors for arsenic-induced skin lesions. Furthermore, folic acid (FA) supplementation does indeed facilitate As elimination and significantly lowers blood As concentrations in individuals who are folate deficient. We have also determined that blood As is a good biomarker of As exposure and is directly associated with the risk for As-induced skin lesions. Collectively, the implication of these findings is that FA has enormous therapeutic potential for ameliorating the long-term health consequences of arsenic exposure for the many populations at risk. However, several fundamental questions remain and will be addressed in this study. This trial is designed to determine 1) whether FA supplementation lowers blood As concentrations in the general Bangladeshi population, 2) at what time point a nadir in blood As is achieved, and 3) whether creatine supplementation, alone or in addition to 400 µg/d FA, will spare methyl groups, resulting in lower blood As, lower homocysteine (Hcys) concentrations, and increased methylation of As. The creatine arms are based on multiple studies that show that urinary creatinine concentrations are a very strong predictor of As methylation. The final step in creatine biosynthesis is the methylation of guanidinoacetate to creatine; this process consumes 50-75% of all SAM-derived methyl groups and is also responsible for 50-75% of all Hcys biosynthesis. Thus, this trial will test the hypothesis that creatine supplementation, which shuts down endogenous creatine biosynthesis, will spare methyl groups, lower Hcys, and increase As methylation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboPlacebo daily |
| Folic Acid 400 ug | Experimental | Dietary Supplement: folic acid400 µg folic acid daily |
| Folic Acid 800 ug | Experimental | Dietary Supplement: folic acid800 µg folic acid daily |
| Creatine | Experimental | Dietary Supplement: creatinecreatine daily |
| Creatine + Folic Acid | Experimental | Dietary Supplement: creatine + folic acidcreatine + folic acid daily |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Currently exposed to arsenic via contaminated drinking water
- Well water arsenic concentration > 10 ug/L
- Between the ages of 20 and 65
Key exclusion criteria (4 listed)
- Women who are currently pregnant or plan to become pregnant within the next 6 months
- Currently taking nutritional supplements
- Known renal disease
- Participation in any other clinical trial
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebodaily, 24 weeks | Other | Placebo |
| folic acid400 ug/d for 12 or 24 weeks | Dietary supplement | Folic Acid 400 ug |
| folic acid800 µg/d for 12 or 24 weeks | Dietary supplement | Folic Acid 800 ug |
| creatine3 mg/d for 12 weeks | Dietary supplement | Creatine |
| creatine + folic acid3 mg creatine/d + 400 µg folic acid/d for 12 weeks | Dietary supplement | Creatine + Folic Acid |
Primary outcome
blood arsenic concentrations
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2012.
- Derived from this study: PubMed 40668877Li W, Wu H, Goldsmith J, Glabonjat RA, Ilievski V, Balac O, Slavkovich V, Pinto-Pacheco B, Lin X, Parvez F, Jackson GL, Siddique AB, Uddin MN, Islam T, Martinez-Morata I, Navas-Acien A, Niedzwiecki MM, Kioumourtzoglou MA, Pierce BL, Graziano JH, Bottiglieri T, Walker DI, Gamble MV. Metabolic Signature of Arsenic Exposure and Metabolism: The Folic Acid and Creatine Trial. Environ Sci Technol. 2025 Jul 29;59(29):14905-14916. doi: 10.1021/acs.est.5c01597. Epub 2025 Jul 16.
- Derived from this study: PubMed 38092151Martinez-Morata I, Wu H, Galvez-Fernandez M, Ilievski V, Bottiglieri T, Niedzwiecki MM, Goldsmith J, Jones DP, Kioumourtzoglou MA, Pierce B, Walker DI, Gamble MV. Metabolomic Effects of Folic Acid Supplementation in Adults: Evidence from the FACT Trial. J Nutr. 2024 Feb;154(2):670-679. doi: 10.1016/j.tjnut.2023.12.010. Epub 2023 Dec 12.
- Derived from this study: PubMed 36976258Abuawad AK, Bozack AK, Navas-Acien A, Goldsmith J, Liu X, Hall MN, Ilievski V, Lomax-Luu AM, Parvez F, Shahriar H, Uddin MN, Islam T, Graziano JH, Gamble MV. The Folic Acid and Creatine Trial: Treatment Effects of Supplementation on Arsenic Methylation Indices and Metabolite Concentrations in Blood in a Bangladeshi Population. Environ Health Perspect. 2023 Mar;131(3):37015. doi: 10.1289/EHP11270. Epub 2023 Mar 28.
- Derived from this study: PubMed 34661903Bae S, Kamynina E, Guetterman HM, Farinola AF, Caudill MA, Berry RJ, Cassano PA, Stover PJ. Provision of folic acid for reducing arsenic toxicity in arsenic-exposed children and adults. Cochrane Database Syst Rev. 2021 Oct 18;10(10):CD012649. doi: 10.1002/14651858.CD012649.pub2.
- Derived from this study: PubMed 32918135Bozack AK, Howe CG, Hall MN, Liu X, Slavkovich V, Ilievski V, Lomax-Luu AM, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Graziano JH, Gamble MV. Betaine and choline status modify the effects of folic acid and creatine supplementation on arsenic methylation in a randomized controlled trial of Bangladeshi adults. Eur J Nutr. 2021 Jun;60(4):1921-1934. doi: 10.1007/s00394-020-02377-z. Epub 2020 Sep 11.
- Derived from this study: PubMed 30590411Bozack 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.
- Derived from this study: PubMed 27052531Hall MN, Howe CG, Liu X, Caudill MA, Malysheva O, Ilievski V, Lomax-Luu AM, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Graziano JH, Gamble MV. Supplementation with Folic Acid, but Not Creatine, Increases Plasma Betaine, Decreases Plasma Dimethylglycine, and Prevents a Decrease in Plasma Choline in Arsenic-Exposed Bangladeshi Adults. J Nutr. 2016 May;146(5):1062-7. doi: 10.3945/jn.115.227132. Epub 2016 Apr 6.
- Derived from this study: PubMed 26311810Peters BA, Hall MN, Liu X, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Ilievski V, Graziano JH, Gamble MV. Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial. J Nutr. 2015 Oct;145(10):2245-52. doi: 10.3945/jn.115.216739. Epub 2015 Aug 26.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mary V Gamble, PhD principal investigator
Columbia University, Department of Environmental Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing folic acid, creatine and creatine + folic acid in people with High Blood Arsenic Due to Chronic Arsenic Exposure, run by Columbia University at 1 site in Bangladesh.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Bangladesh. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
blood arsenic concentrations (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01050556, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2012; AzTrials last refreshed its copy on 8 Nov 2026.