Folic Acid Handling by the Human Gut: Implications for Food Fortification and Supplementation
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 6
- Locations
- 4
- Primary Endpoint
- The percentage of folate in un-modified and modified form in the portal vein for each of the different oral folate dosing formulations
Study Overview
Brief Summary
The aim of this study is to test the assumption that, in humans, folic acid, a dietary supplement is biotransformed (reduced and methylated) to the natural circulating plasma folate 6S-5Methyltetrahydrofolic acid (5-MTHF) in the intestinal mucosa.
Detailed Description
Current thinking, based mainly on rodent studies, is that physiological doses of folic acid (pteroylmonoglutamic acid), like dietary vitamin folates, are biotransformed in the intestinal mucosa and transferred to the portal vein as the natural circulating plasma folate, 5-methyltetrahydrofolic acid (5-MTHF), before entering the liver and the wider systemic blood supply.
Study design:Open labelled study that samples portal and peripheral veins for labelled folate concentrations following oral ingestion with physiological doses of dietary supplements stable-isotope-labelled folic acid, or, the reduced folate, 5-formyltetrahydrofolic acid (5-FormylTHF). The study was performed in subjects with a Transjugular Intrahepatic Porto Systemic Shunt (TIPSS) in situ at the time of a routine annual patency check to allow blood samples to be taken from the portal vein. The aim of this study is to test the assumption that, in humans, folic acid is biotransformed (reduced and methylated) to 5-MTHF in the intestinal mucosa.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Stable, synthetic liver function without recent evidence of decompensation (defined as liver function inadequacy or active complications of portal hypertension)
- •Abstinent from alcohol
- •Free from malignant disease
- •Normal gut permeability (as assessed by the lactulose/mannitol test)
- •Patent TIPSS on their last surveillance
Exclusion Criteria
- •Taking Vitamin B supplements
- •Taking Folic Acid supplementation
- •Unable to provide informed consent
Arms & Interventions
13C5-folic acid or 13C5-6S-5-FormylTHF
Physiological 500 nmol (220 µg folic acid equivalent) dose of dietary supplement 13C5-folic acid or 13C5-6S-5-FormylTHF given to subjects with in situ transjugular intrahepatic portosystemic stent at the time of routine venography patency check followed by regular portal venous sampling for 85 minutes at pre determined intervals and then physiological 500 nmol dose of 13C-6S-5-FormylTHF or 13C5-folic acid respectively at the next annual routine venography patency check followed by portal venous sampling for 85 minutes
Intervention: 13C5-folic acid or 13C5-6S-5-FormylTHF (Dietary Supplement)
Outcomes
Primary Outcomes
The percentage of folate in un-modified and modified form in the portal vein for each of the different oral folate dosing formulations
Time Frame: 85 minutes
Secondary Outcomes
No secondary outcomes reported