Where is the Initial Site of Biotransformation of Folates in Humans?

Not Applicable

Completed

• Conditions: Healthy
• Interventions: Dietary Supplement: 13C5-folic acid or 13C5-6S-5-FormylTHF

• Registration Number: NCT02135393
• Lead Sponsor: Newcastle-upon-Tyne Hospitals NHS Trust

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 Timeline

• Study Start: 2009-04
• Primary Completion: 2011-09
• Study Completion: 2011-09
• Status Verified: 2014-05
• Study First Submitted: 2014-05-08
• Study First Submitted QC: 2014-05-08
• Last Update Submitted: 2014-05-08
• Study First Posted: 2014-05-09
• Last Update Posted: 2014-05-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
13C5-folic acid or 13C5-6S-5-FormylTHF	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

Primary Outcome Measures

Name	Time	Method
The percentage of folate in un-modified and modified form in the portal vein for each of the different oral folate dosing formulations	85 minutes

Trial Locations

Locations (2)

Institute of Food Research; 🇬🇧 Norwich, United Kingdom

Freeman Hospital; 🇬🇧 Newcastle Upon Tyne, Tyneside, United Kingdom