Folate is absorbed across the human colon: evidence by using enteric-coated caplets containing 13C-labeled [6S]-5-formyltetrahydrofolate

Am J Clin Nutr. 2014 Nov;100(5):1278-86. doi: 10.3945/ajcn.114.091785. Epub 2014 Sep 3.


Background: Folate intakes that do not meet or greatly exceed requirements may be associated with negative health outcomes. A better understanding of contributors that influence the input side will help establish dietary guidance that ensures health benefits without associated risks. Colonic microbiota produce large quantities of folate, and [(13)C5]5-formyltetrahydrofolate infused during colonoscopy is absorbed. However, it is unclear if significant quantities of folate are absorbed in an intact microbiome.

Objective: We determined whether and how much of a physiologic dose of [(13)C5]5-formyltetrahydrofolate delivered in a pH-sensitive enteric caplet to an intact colonic microbiome is absorbed.

Design: Healthy adults ingested a specially designed pH-sensitive acrylic copolymer-coated barium sulfate caplet that contained 855 nmol (400 μg) [(13)C5]5-formyltetrahydrofolate. After a washout period ≥ 4 wk, subjects received an intravenous injection of the same compound (214 nmol). Serially collected blood samples before and after each test dose were analyzed by using a microbiological assay and liquid chromatography-tandem mass spectrometry.

Results: Caplet disintegration in the colon was observed by fluoroscopic imaging for 6 subjects with a mean (± SD) complete disintegration time of 284 ± 155 min. The mean (± SEM) rate of appearance of [(13)C5]5-methyltetrahydrofolate in plasma was 0.33 ± 0.09 (caplet) and 5.8 ± 1.2 (intravenous) nmol/h. Likely because of the significant time in the colon, the mean apparent absorption across the colon was 46%.

Conclusions: Folate is absorbed across the colon in humans with an undisturbed microbiome. This finding and previous observations of the size of the colonic depot of folate and its potential for manipulation by diet (eg, dietary fiber, oligosaccharides, and probiotics) suggest that an individual's dietary folate requirement may differ depending on the consumption of dietary constituents that affect the size and composition of their gastrointestinal microbiota. In addition, a systematic investigation of the role of colonic folate on gastrointestinal development and the prevention of colorectal cancer is warranted. This trial was registered at as NCT00941174.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Carbon Isotopes
  • Chromatography, Liquid
  • Colon / metabolism*
  • Diet
  • Dose-Response Relationship, Drug
  • Drug Compounding
  • Female
  • Healthy Volunteers
  • Humans
  • Hydrogen-Ion Concentration
  • Leucovorin / administration & dosage
  • Leucovorin / blood
  • Leucovorin / pharmacokinetics*
  • Male
  • Middle Aged
  • Tandem Mass Spectrometry
  • Young Adult


  • Carbon Isotopes
  • Leucovorin

Associated data