Jimi S, Koizumi S, Sato K, Miyazaki M, Saparov A. Collagen-derived dipeptide Pro-Hype administration accelerates muscle regenerative healing accompanied by less scarring after wounding on the abdominal wall in mice. Sci Rep.2021;11(1):18750. doi:10.1038/s41598-021-98407-9.

Clinical trial; free drinking for 21 days

Mice with abdominal surgery

• Casein
• High molecular weight collagen peptides
• Low molecular weight collagen peptides, including Pro-Hyp and
• Hyp-Gly

Pro-Hyp administration accelerated muscle regenerative healing, accompanied by less scarring, after wounding of the abdominal wall. Pro-Hyp could be administered to patients with
pressure injuries, who have undergone surgery or have trauma to help activate the wound-healing process.

Lee SK, Posthauer ME, Dorner B, Redovian V, Maloney MJ. Pressureulcer healing with a concentrated, fortified, collagen protein hydrolysate supplement: a randomized controlled trial. Adv Skin Wound Care. 2006;19(2): 92-96. doi:10.1097/00129334-200603000-00011.

Randomized trial for 8 weeks at 23 longterm care facilities in four states

89 residents with stage 2, 3, or 4 pressure injuries; 71 completed the study

• Standard care plus a concentrated, fortified, collagen protein hydrolysate supplement
• Standard care plus placebo
• Three times daily for 8 weeks

Residents who received standard care plus the concentrated, fortified, collagen protein hydrolysate supplement had significantly better PUSH tool scores compared to those who had
standard care plus placebo.

Sato K, Asai TT, Jimi S. Collagen-derived di-peptide, prolylhydroxyproline (Pro-Hyp): a new low molecular weight growth-initiating factor for specific fibroblasts associated with wound healing. Front Cell Dev Biol. 2020;8:543975. doi:10.3389/fcell.2020.548975.

Review

Animal studies and human clinical trials

• Pro-Hyp

Ingestion of collagen hydrolysate enhances wound healing, especially diabetes-induced chronic wounds and pressure injuries. Pro-Hyp is a low molecular weight growth-initiating factor for specific fibroblasts that are involved in the wound healing process.

Skov K, Oxfeldt M, Thögersen R, Hansen M, Bertram HC. Enzymatic hydrolysis of a collagen hydrolysate enhances postprandial absorption rate—a randomized controlled trial. Nutrients. 2019;11(5):1064. doi:10.3390/nu11051064.

Randomized, blinded, cross-over trial

Ten healthy males, ages 18-35 years

• EHC protein
• Non-EHC protein
• Placebo
• 3 nonconsecutive days

Enzymatic hydrolysis of collagen is associated with enhanced absorption of glycine, proline, and hydroxyproline 20 minutes post-ingestion. Also, a greater AUC for glycine, proline,
and hydroxyproline for an EHC hydrolysate suggested a higher bioavailability for EHC compared to a nonenzymatically hydrolyzed collagen hydrolysate.

Sugihara F, Inoue N, Venkateswarathirukumara S. Ingestion of bioactive collagen hydrolysates enhanced pressure ulcer healing in a randomized double-blind placebo-controlled clinical study. Sci Rep. 2018;8(1):11403. doi:10.1038/s41598-018-29831-7.

Double-blind, placebo controlled clinical study

Subjects with pressure injuries, stage II or III; 112 subjects completed the study

• Low level Pro-Hyp and Hyp-Gly collagen hydrolysate
• High level Pro-Hyp and Hyp-Gly collagen hydrolysate
• Placebo
• 16 weeks

Collagen hydrolysate with higher levels of Pro-Hyp and Hyp-Gly helps heal pressure injuries as measured by improvement in PUSH and PSST scores.