Generation of bioactive prolyl‐hydroxyproline (Pro‐Hyp) by oral administration of collagen hydrolysate and degradation of endogenous collagen

Hydroxyproline‐containing di‐ and tripeptides increase in human blood plasma after ingestion of collagen hydrolysate in a dose‐dependent manner. Prolyl‐hydroxyproline (Pro‐Hyp) and hydroxyprolyl‐glycine (Pro‐Gly) are the main food‐derived collagen peptides present in human blood plasma. Pro‐Hyp increases the number of fibroblasts migrating from the mouse skin and enhances the growth of fibroblasts attached to the collagen gel. Pro‐Hyp is also generated from endogenous collagen in the granulation tissue in mice skin and ear with dermatitis, while it does not increase in the normal tissues of the same animal. However, Hyp‐Gly does not increase in all tissues. These facts indicate that Pro‐Hyp is generated by the degradation of endogenous collagen to activate cells involved in tissue reconstruction. Orally administered Pro‐Hyp is deposited in animal organs even after clearance of Pro‐Hyp from blood. Thus, the endogenous bioactive peptide can be provided by ingestion of collagen hydrolysate.