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

Newcastle-upon-Tyne Hospitals NHS Trust6 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Healthy

Interventions

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

Eligibility

Sex: ALLHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (2)

Freeman Hospital

Newcastle upon Tyne, Tyneside, United Kingdom

Institute of Food Research

Norwich, United Kingdom

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

Data from ClinicalTrials.gov

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