Digestive fate of dietary carrageenan: Evidence of interference with digestive proteolysis and disruption of gut epithelial function

Mol Nutr Food Res. 2017 Mar;61(3). doi: 10.1002/mnfr.201600545. Epub 2017 Jan 25.


Scope: The objective of this study was to interrogate two mechanisms by which commercial Carrageenans (E407) (CGN) may adversely affect human health: (i) Through modification of gastric proteolysis and (ii) Through affecting gut epithelial structure and function.

Methods and results: Three commercial CGN samples with distinct zeta-potentials (stable at the pH range of 3-7 and varied with physiological levels of CaCl2 ) were mixed with milk, soy or egg protein isolates, then subjected to a semi-dynamic in vitro digestion model and analyzed by SDS-PAGE. This revealed varying levels of interference with gastric digestive proteolysis and a significant decrease in pepsin activity. Further, a Caco-2 cell model was used to explore various effects of physiologically digested CGN (pdCGN) on various epithelial cell functions and characteristics. Samples of pdCGN (0.005-0.5 mg/mL) affected the epithelial barrier function, including redistribution of the tight-junction protein Zonula Occludens (Zo)-1, changes in cellular F-actin architecture and increased monolayer permeability to the transfer of macromolecules. Moreover, pdCGN induced elevation in the levels of the pro-inflammatory IL-8 receptor CXCR1.

Conclusion: This work raises the possibility that CGN may reduce protein and peptide bioaccessibility, disrupt normal epithelial function, promote intestinal inflammation, and consequently compromise consumer health.

Keywords: Carrageenan; Digestive proteolysis; Epithelial tight junctions; Intestinal epithelium; Intestinal inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Carrageenan / adverse effects*
  • Carrageenan / chemistry
  • Carrageenan / pharmacokinetics*
  • Digestion
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / ultrastructure
  • Food Additives / adverse effects
  • Food Additives / pharmacokinetics
  • Humans
  • Intestinal Mucosa / cytology*
  • Intestinal Mucosa / drug effects
  • Proteolysis
  • Receptors, Interleukin-8A / genetics
  • Receptors, Interleukin-8A / metabolism
  • Zonula Occludens-1 Protein / metabolism


  • Food Additives
  • Receptors, Interleukin-8A
  • TJP1 protein, human
  • Zonula Occludens-1 Protein
  • Carrageenan