Folic Acid and Creatine as Therapeutic Approaches for Lowering Blood Arsenic
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.
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
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Conditions
High Blood Arsenic Due to Chronic Arsenic Exposure
Intervention
Placebo, folic acid, folic acid, creatine, creatine + folic acid
Location
Columbia University Arsenic Research Project
Dhaka
Bangladesh
Status
Not yet recruiting
Source
Columbia University
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01050556
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-08-27T03:16:34-0400
Clinical Trials
Bioavailability Study of Folic Acid in Healthy Women
The purpose of the study is to determine the bioavailability of orally administered folic acid compared with the i.v. administered folic acid, and to use the samples collected to validate ...
The purpose of the study is to determine the bioequivalence of Norgestimate (NGM) and Ethinyl Estradiol (EE) in 2 formulations of 250 mcg NGM/25 mcg EE, 1 without folic acid and 1 containi...
High levels of homocysteine, which is an amino acid in the blood, have been linked to an increased risk of heart disease. This study will examine the effect that differing levels of folic ...
Folic Acid and Vitamin B12 in Young Indian Children
Hypothesis: Supplementation of two recommended daily allowances (RDA) of folic acid with or without simultaneous administration of vitamin B12 reduces the rates of acute lower respiratory ...
Multi-micronutrient Supplementation During Peri-conception and Congenital Heart Disease
The purpose of this study is to determine whether daily oral supplements of vitamin B complex along with folic acid or supplements of iron plus folic acid given to women during peri-concep...
PubMed Articles
Backgrounds Folic acid dose at ≦5 mg/week has been recommended for rheumatoid arthritis (RA) patients to decrease risk of methotrexate adverse effects. However, higher doses of folic acid is used ...
Binding efficacy of tRNA with folic acid-PAMAM nanoparticles.
tRNA binding efficacy to folic acid-PAMAM nanoparticles was determined, using multiple spectroscopic methods, thermodynamic analysis and transmission electron microscopy (TEM). The structural analysis...
Is folic acid safe for non-muscle-invasive bladder cancer patients? An evidence-based cohort study.
Patients with cancer are highly concerned about food choices and dietary supplements that may affect their treatment outcomes. Excess folic acid (synthetic folate) from supplements or fortification ca...
Combined Prenatal Pesticide Exposure and Folic Acid Intake in Relation to Autism Spectrum Disorder.
Maternal folic acid (FA) protects against developmental toxicity from certain environmental chemicals.
Efficacy of Folic Acid Therapy in Patients with Hyperhomocysteinemia.
Increased plasma homocysteine (Hcy) levels are a risk factor for stroke and can be reduced with folic acid therapy. Therefore, it is extremely important for patients with hyperhomocysteinemia (HHcy) t...
Medical and Biotech [MESH] Definitions
Leucovorin
The active metabolite of FOLIC ACID. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid.
Folate Receptors, Gpi-anchored
Cell surface receptors that bind to and transport FOLIC ACID, 5-methyltetrahydrofolate, and a variety of folic acid derivatives. The receptors are essential for normal NEURAL TUBE development and transport folic acid via receptor-mediated endocytosis.
Pteroylpolyglutamic Acids
Derivatives of folic acid (pteroylglutamic acid). In gamma-glutamyl linkage they are found in many tissues. They are converted to folic acid by the action of pteroylpolyglutamate hydrolase or synthesized from folic acid by the action of folate polyglutamate synthetase. Synthetic pteroylpolyglutamic acids, which are in alpha-glutamyl linkage, are active in bacterial growth assays.
Folic Acid Deficiency
A nutritional condition produced by a deficiency of FOLIC ACID in the diet. Many plant and animal tissues contain folic acid, abundant in green leafy vegetables, yeast, liver, and mushrooms but destroyed by long-term cooking. Alcohol interferes with its intermediate metabolism and absorption. Folic acid deficiency may develop in long-term anticonvulsant therapy or with use of oral contraceptives. This deficiency causes anemia, macrocytic anemia, and megaloblastic anemia. It is indistinguishable from vitamin B 12 deficiency in peripheral blood and bone marrow findings, but the neurologic lesions seen in B 12 deficiency do not occur. (Merck Manual, 16th ed)
Folic Acid Transporters
Proteins involved in the transport of FOLIC ACID and folate derivatives across the CELLULAR MEMBRANE.
