Impact of High-dose Folic Acid Supplementation on Pathways Linked to DNA Formation
This study is not yet open for participant recruitment.
Verified November 2012 by University of British Columbia
Sponsor:
University of British Columbia
Information provided by (Responsible Party):
University of British Columbia
ClinicalTrials.gov Identifier:
NCT01687127
First received: September 13, 2012
Last updated: November 22, 2012
Last verified: November 2012
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Purpose
Periconceptional supplementation with folic acid - the synthetic form of the B-vitamin folate - reduces the occurrence of adverse pregnancy outcomes such as spina bifida. The underlying biochemical mechanisms for how folic acid affects health outcomes however are unknown. The naturally occurring form 5-methyltetrahydrofolate (5-MTHF) is now available and discussed as an adequate substitute to folic acid. This study aims to determine the effect of folic acid compared to 5-MTHF on cellular mechanisms. Stable isotope tracer protocols will be used that allow determining the effect of folic acid on the dynamics of metabolic pathways in the human body.
Hypothesis: Supplementation with high-dose folic acid alters the turnover rate of folate dependent pathways in healthy humans; but 5-MTHF does not. Genetic variations in a key enzyme of the folate metabolism will aggravate the effect of folic acid on the metabolic pathways.
| Condition | Intervention |
|---|---|
|
One-carbon Metabolism in Healthy Individuals |
Dietary Supplement: Folic acid Dietary Supplement: 5-methyltetrahydrofolate, calcium salt |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Basic Science |
| Official Title: | Metabolic Consequences of High-Dose Folic Acid Supplementation on Kinetics of 1-Carbon Metabolism |
Resource links provided by NLM:
Further study details as provided by University of British Columbia:
Primary Outcome Measures:
- Plateau enrichment of infused amino acid tracers and related metabolites to quantify turnover rates of folate dependent pathways [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 25 |
| Study Start Date: | January 2013 |
| Estimated Study Completion Date: | December 2015 |
| Estimated Primary Completion Date: | March 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Folic acid supplementation
Folic acid will be given orally in form of tablets. A supplement of 1 mg will be taken daily for 12 weeks. Thereafter, a supplement of 5 mg will be taken daily for 12 weeks (i.e., until Week 24). At baseline, Week 12, and Week 24, subjects will receive a 9-hour primed constant infusion of amino acids in saline solution for quantification of kinetics of one-carbon metabolism.
|
Dietary Supplement: Folic acid
Other Name: Pteroylmonoglutamic acid
|
|
Experimental: 5-MTHF supplementation
The calcium salt of 5-methyltetrahydrofolate (5-MTHF; Brand name "Metafolin") will be given orally in form of tablets. A supplement of 1 mg will be taken daily for 12 weeks. Thereafter, a supplement of 5 mg will be taken daily for 12 weeks (i.e., until Week 24). At baseline, Week 12, and Week 24, subjects will receive a 9-hour primed constant infusion of amino acids in saline solution for quantification of kinetics of one-carbon metabolism.
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Dietary Supplement: 5-methyltetrahydrofolate, calcium salt
Other Names:
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Eligibility| Ages Eligible for Study: | 20 Years to 35 Years |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | Yes |
Criteria
Inclusion Criteria:
- Generally healthy
- Body mass index of between 19-24 kg/m2
- Normal folate, vitamin B12, and B6 status
Exclusion Criteria:
- Unable to swallow tablets
- Unable to receive intravenous catheters
- Use of vitamin supplements, amino acid or protein supplements for more than six months before study participation
- Chronic consumption of a high-protein diet (e.g. Atkins Diet)
- Medical conditions such as diabetes, asthma, cancer, cardiovascular disease, a history of neural tube defect (such as spina bifida) affected pregnancy, have had gastrointestinal surgery, abnormal kidney, thyroid function, or psychiatric illness, or any other chronic disease
- Pregnancy or lactation
- Smoking, use of recreational drugs, and/or consumption of more than one alcohol drink per day or more than seven per week.
- Use of long-term prescription medication such as hormonal contraceptives, antidepressants, anticonvulsants, anticoagulants, or other chronic medication
- Blood donation in the last three months prior to study start
- Unable to provide informed consent, or unable to read and write English
- Low compliance to intervention as determined by early steady-state or reduction in blood folate concentrations
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01687127
Contacts
| Contact: Theresa H Schroder, Dipl. | 604-822-1250 | schrod10@mail.ubc.ca |
| Contact: Yvonne Lamers, PhD | 604-822-1490 | yvonne.lamers@ubc.ca |
Locations
| Canada, British Columbia | |
| Children's and Women's Health Centre of BC (incl. Sunny Hill), Child and Family Research Institute | Not yet recruiting |
| Vancouver, British Columbia, Canada, V5Z 4H4 | |
| Contact: Theresa H Schroder, Dipl 604-822-1250 folate.study@ubc.ca | |
| Sub-Investigator: Jehannine C Austin, PhD | |
| Sub-Investigator: Amanda Skoll, MD, FRCSC | |
Sponsors and Collaborators
University of British Columbia
Investigators
| Principal Investigator: | Yvonne Lamers, PhD | University of British Columbia |
More Information
No publications provided
| Responsible Party: | University of British Columbia |
| ClinicalTrials.gov Identifier: | NCT01687127 History of Changes |
| Other Study ID Numbers: | H11-03009, CIHR Application Nr. 247226 |
| Study First Received: | September 13, 2012 |
| Last Updated: | November 22, 2012 |
| Health Authority: | Canada: Health Canada |
Keywords provided by University of British Columbia:
|
folic acid folate 5-methyltetrahydrofolate supplements women |
one-carbon metabolism methionine DNA methylation in vivo kinetics |
Additional relevant MeSH terms:
|
Folic Acid Vitamin B Complex Hematinics Vitamins Micronutrients |
Growth Substances Physiological Effects of Drugs Pharmacologic Actions Hematologic Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 22, 2013