Clinical trial NCT02135393: Where is the Initial Site of Biotransformation of Folates in Humans?
Official title: Folic Acid Handling by the Human Gut: Implications for Food Fortification and Supplementation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Lead sponsor: Newcastle-upon-Tyne Hospitals NHS Trust
Sponsor class: OTHER
Collaborators: name: Quadram Institute Bioscience
name: University of Nottingham
First posted: 2014-05-09
Enrollment: 6
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: The percentage of folate in un-modified and modified form in the portal vein for each of the different oral folate dosing formulations
timeFrame: 85 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
state: Tyneside
city: Norwich
country: United Kingdom
facility: Institute of Food Research
Study officials:
affiliation: Newcastle University
name: David E Jones, PhD FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Patanwala I, King MJ, Barrett DA, Rose J, Jackson R, Hudson M, Philo M, Dainty JR, Wright AJ, Finglas PM, Jones DE. Folic acid handling by the human gut: implications for food fortification and supplementation. Am J Clin Nutr. 2014 Aug;100(2):593-9. doi: 10.3945/ajcn.113.080507. Epub 2014 Jun 18.