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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Healthy

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Freeman Hospital, Newcastle upon Tyne, Tyneside, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

13C5-folic acid or 13C5-6S-5-FormylTHF

Dietary Supplement

Subjects with an insitu transjugular intrahepatic porto systemic stent shunt assigned to receive either a physiological 500 nmol (220 µg folic acid equivalent) dose of 13C5-folic acid or 13C5-6S-5-FormylTHF at the time of routine shunt venography to check patency followed by portal venous sampling at pre defined time points for 85 minutes and then given 13C5-6S-5-FormylTHF ator 13C5-folic acid at their next annual venography patency check with portal venous sampling at pre defined time points for 85 minutes

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

Sponsors and collaborators

Lead sponsor

Newcastle-upon-Tyne Hospitals NHS Trust

Other

Collaborators

Quadram Institute Bioscience
University of Nottingham

Registry information

Official study title

Folic Acid Handling by the Human Gut: Implications for Food Fortification and Supplementation

Acronym: FOLTIPS

Important dates

Study start: 2009
Primary completion: 2011
Study completion: 2011
First posted: May 9, 2014
Registry last updated: May 9, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed