Scientific Publications
Folic acid handling by the human gut: Implications for food fortification and supplementation
American Journal of Clinical Nutrition, 100, 593-599
Background: Current thinking, based mainly on rodent studies, is that physiological doses of folic acid (pterylmonoglutamic 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. Objectives: The aim of this study was to test the assumption that, in humans, folic acid is biotransformed (reduced and methylated) to 5-MTHF in the intestinal mucosa. Design: Cross-over study that sampled portal and peripheral veins for labelled folate concentrations following oral ingestion with physiological doses of stable-isotope-labelled folic acid, or, the reduced folate, 5-formyltetrahydrofolic acid (5-FormylTHF) in six subjects with a Transjugular Intrahepatic Porto Systemic Shunt (TIPSS) in situ. The TIPSS allowed blood samples to be taken from the portal vein. Results: Fifteen minutes after a dose of folic acid, 80±12% of labelled folate in the hepatic portal vein was unmodified folic acid. In contrast, following a dose of labelled 5-FormylTHF, only 4±18% of labelled folate in the portal vein was unmodified 5-FormylTHF; the rest having been methylated to 5-MTHF after 15 minutes (post-dose). Conclusions: The human gut appears to have very efficient methylation capacity for dietary folates but limited ability to reduce folic acid. Large amounts of unmodified folic acid in the portal vein are, therefore, probably due to extremely limited mucosal cell dihydrofolate reductase (DHFR) capacity necessary to produce tetrahydrofolic acid prior to sequential methylation to 5-MTHF. This would suggest that humans are reliant on the liver for folic acid reduction even though it has low and highly variable DHFR activity. Chronic liver exposure to folic acid in humans may, therefore, induce saturation, possibly explaining reports of systemic circulation of unmetabolised folic acid.
American Journal of Clinical Nutrition, 100, 593-599
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