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

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02135393

Acronym

FOLTIPS

Enrollment

Registered

2014-05-09

Start date

2009-04-30

Completion date

2011-09-30

Last updated

2014-05-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

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.

Interventions

DIETARY_SUPPLEMENT13C5-folic acid or 13C5-6S-5-FormylTHF

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

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

Design outcomes

Primary

Measure	Time frame
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

Countries

United Kingdom

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026