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

Healthy Clinical Trial

— FOLTIPS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02135393
• Other study ID #: UK CRN 5085
• Status: Completed
• Phase: N/A
• First received: May 8, 2014
• Last updated: May 8, 2014
• Start date: April 2009
• Est. completion date: September 2011

Study information

• Verified date: May 2014
• Source: Newcastle-upon-Tyne Hospitals NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: National Health ServiceUnited Kingdom: National Institute for Health ResearchUnited Kingdom: Research Councils UK
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A and older

Eligibility

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

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy

Intervention

Dietary Supplement:
• 13C5-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

Locations

Country	Name	City	State
United Kingdom	Freeman Hospital	Newcastle Upon Tyne	Tyneside
United Kingdom	Institute of Food Research	Norwich

Sponsors (3)

Lead Sponsor	Collaborator
Newcastle-upon-Tyne Hospitals NHS Trust	Institute of Food Research, University of Nottingham

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No