Where is the Initial Site of Biotransformation of Folates in Humans? (FOLTIPS)

Newcastle-upon-Tyne Hospitals NHS Trust

Status: Completed

Conditions: Healthy

Treatments: Dietary Supplement: 13C5-folic acid or 13C5-6S-5-FormylTHF

Study type: Interventional

Funder types: Other

Identifiers

NCT02135393

UK CRN 5085

Details and patient eligibility

About

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.

Full 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.

Enrollment: 6 patients

Sex: All

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

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

Experimental group

Description:

Physiological 500 nmol (220 µg folic acid equivalent) dose of dietary supplement 13C5-folic acid or 13C5-6S-5-FormylTHF given to subjects with in situ transjugular intrahepatic portosystemic stent at the time of routine venography patency check followed by regular portal venous sampling for 85 minutes at pre determined intervals and then physiological 500 nmol dose of 13C-6S-5-FormylTHF or 13C5-folic acid respectively at the next annual routine venography patency check followed by portal venous sampling for 85 minutes

Treatment:

Dietary Supplement: 13C5-folic acid or 13C5-6S-5-FormylTHF