The intestinal absorption of folates

Annu Rev Physiol. 2014:76:251-74. doi: 10.1146/annurev-physiol-020911-153251.


The properties of intestinal folate absorption were documented decades ago. However, it was only recently that the proton-coupled folate transporter (PCFT) was identified and its critical role in folate transport across the apical brush-border membrane of the proximal small intestine established by the loss-of-function mutations identified in the PCFT gene in subjects with hereditary folate malabsorption and, more recently, by the Pcft-null mouse. This article reviews the current understanding of the properties of PCFT-mediated transport and how they differ from those of the reduced folate carrier. Other processes that contribute to the transport of folates across the enterocyte, along with the contribution of the enterohepatic circulation, are considered. Important unresolved issues are addressed, including the mechanism of intestinal folate absorption in the absence of PCFT and regulation of PCFT gene expression. The impact of a variety of ions, organic molecules, and drugs on PCFT-mediated folate transport is described.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Enterohepatic Circulation / physiology
  • Folic Acid / metabolism*
  • Folic Acid Deficiency / genetics
  • Folic Acid Deficiency / metabolism
  • Humans
  • Intestinal Absorption / genetics
  • Intestinal Absorption / physiology*
  • Intestine, Large / metabolism
  • Intestine, Small / metabolism
  • Malabsorption Syndromes / genetics
  • Malabsorption Syndromes / metabolism
  • Mice
  • Proton-Coupled Folate Transporter / genetics
  • Proton-Coupled Folate Transporter / metabolism


  • Proton-Coupled Folate Transporter
  • Folic Acid

Supplementary concepts

  • Folate Malabsorption, Hereditary