A Pilot Study for the Detection of Cyclic Prolyl-Hydroxyproline (Pro-Hyp) in Human Blood after Ingestion of Collagen Hydrolysate

Nutrients. 2018 Sep 22;10(10):1356. doi: 10.3390/nu10101356.


Levels of short linear hydroxyproline (Hyp)-containing peptides, such as prolyl-hydroxyproline (Pro-Hyp), increase in human blood after the ingestion of collagen hydrolysate, which has been associated with beneficial effects for human skin and joints. The present study demonstrates the presence of a novel food-derived collagen peptide, cyclic Pro-Hyp, in human blood after the ingestion of collagen hydrolysate. The cyclic Pro-Hyp levels in plasma samples were estimated by liquid chromatography mass spectrometry (LC-MS). Cyclic Pro-Hyp levels significantly increased in the plasma after ingestion of collagen hydrolysate, reaching a maximum level after 2 h and then decreasing. The maximum level of cyclic Pro-Hyp in plasma ranged from 0.1413 to 0.3443 nmol/mL, representing approximately 5% of linear Pro-Hyp in plasma after ingestion of collagen hydrolysate. Addition of cyclic Pro-Hyp in medium at 7 nmol/mL significantly enhanced the growth rate of mouse skin fibroblasts on collagen gel more extensively compared to linear Pro-Hyp.

Keywords: Pro-Hyp; collagen hydrolysate; collagen peptides; cyclic Pro-Hy; fibroblasts; mouse skin.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Animals
  • Collagen / administration & dosage
  • Collagen / blood
  • Collagen / pharmacology*
  • Dipeptides / blood*
  • Eating
  • Female
  • Fibroblasts / drug effects
  • Gelatin
  • Humans
  • Hydroxyproline / blood*
  • Mice
  • Middle Aged
  • Peptides / administration & dosage
  • Peptides / blood*
  • Peptides / pharmacology
  • Pilot Projects
  • Protein Hydrolysates / administration & dosage
  • Protein Hydrolysates / blood
  • Protein Hydrolysates / pharmacology*
  • Skin*
  • Sus scrofa
  • Tandem Mass Spectrometry


  • Dipeptides
  • Peptides
  • Protein Hydrolysates
  • prolyl-4-hydroxyproline
  • Gelatin
  • Collagen
  • Hydroxyproline