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| ID | Type | Description | Link |
|---|---|---|---|
| CIHR Application Nr. 247226 | Other Grant/Funding Number | Canadian Institutes of Health Research - Application Nr. 247226 |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Folic acid supplementation | Experimental | 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. |
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| 5-MTHF supplementation | Experimental | 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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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Folic acid | Dietary Supplement | Supplement |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plateau enrichment of infused amino acid tracers and related metabolites to quantify turnover rates of folate dependent pathways | 24 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yvonne Lamers, PhD | Contact | 604-827-1776 | yvonne.lamers@ubc.ca | |
| Amy McMahon, PhD | Contact | 604-822-1250 | amy.mcmahon@ubc.ca |
| Name | Affiliation | Role |
|---|---|---|
| Yvonne Lamers, PhD | University of British Columbia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's and Women's Health Centre of BC (incl. Sunny Hill), Child and Family Research Institute | Vancouver | British Columbia | V5Z 4H4 | Canada |
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| ID | Term |
|---|---|
| D005492 | Folic Acid |
| D002955 | Leucovorin |
| C005984 | 5-methyltetrahydrofolate |
| C569381 | levomefolate calcium |
| ID | Term |
|---|---|
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| 5-methyltetrahydrofolate, calcium salt | Dietary Supplement | Supplement |
|
|
| D006571 | Heterocyclic Compounds |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |