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

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

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.

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