Working... Menu

Folic Acid and Creatine as Therapeutic Approaches for Lowering Blood Arsenic (FACTA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01050556
Recruitment Status : Completed
First Posted : January 15, 2010
Last Update Posted : August 1, 2012
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mary Gamble, Columbia University

Brief 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.

Condition or disease Intervention/treatment Phase
High Blood Arsenic Due to Chronic Arsenic Exposure Other: Placebo Dietary Supplement: folic acid Dietary Supplement: creatine Dietary Supplement: creatine + folic acid Phase 4

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Folic Acid and Creatine as Therapeutic Approaches for Lowering Blood Arsenic
Study Start Date : September 2010
Actual Primary Completion Date : June 2011
Actual Study Completion Date : June 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo daily
Other: Placebo
daily, 24 weeks

Experimental: Folic Acid 400 ug
400 µg folic acid daily
Dietary Supplement: folic acid
400 ug/d for 12 or 24 weeks

Experimental: Folic Acid 800 ug
800 µg folic acid daily
Dietary Supplement: folic acid
800 µg/d for 12 or 24 weeks

Experimental: Creatine
creatine daily
Dietary Supplement: creatine
3 mg/d for 12 weeks

Experimental: Creatine + Folic Acid
creatine + folic acid daily
Dietary Supplement: creatine + folic acid
3 mg creatine/d + 400 µg folic acid/d for 12 weeks

Primary Outcome Measures :
  1. blood arsenic concentrations [ Time Frame: 24 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   20 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Currently exposed to arsenic via contaminated drinking water
  • Well water arsenic concentration > 10 ug/L
  • Between the ages of 20 and 65

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01050556

Layout table for location information
Columbia University Arsenic Research Project
Dhaka, Bangladesh
Sponsors and Collaborators
Columbia University
National Cancer Institute (NCI)
Layout table for investigator information
Principal Investigator: Mary V Gamble, PhD Columbia University, Department of Environmental Health Sciences

Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Mary Gamble, Associate Professor of Environmental Health Sciences, Columbia University Identifier: NCT01050556     History of Changes
Other Study ID Numbers: AAAC8618
R01CA133595 ( U.S. NIH Grant/Contract )
First Posted: January 15, 2010    Key Record Dates
Last Update Posted: August 1, 2012
Last Verified: July 2012

Keywords provided by Mary Gamble, Columbia University:
folic acid

Additional relevant MeSH terms:
Layout table for MeSH terms
Folic Acid
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs