Tripeptide-29 (Collagen Hexapeptide)

Also known as: Glycyl-prolyl-hydroxyproline, Gly-Pro-Hyp, GPH peptide, Collagen Tripeptide

Evidence: Preclinical

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Overview

Collagen-derived tripeptide Gly-Pro-Hyp; it preserved collagen I gene expression in stressed fibroblasts in vitro and oral dosing reduced UV skin damage in mice. No topical study exists.

Tripeptide-29 is the INCI name for glycyl-prolyl-hydroxyproline, the repeating unit of the collagen triple helix (PubChem lists Tripeptide-29 as a synonym). The product name's 'Collagen Hexapeptide' is wrong: this is a three-residue peptide. Nearly all research on it comes from oral collagen supplements: it appears in human blood after collagen hydrolysate is eaten (Yazaki et al., 2017), its oral bioavailability in rats is 4.4% (Won et al., 2024), and oral Gly-Pro-Hyp reduced UV skin damage in mice (Yang et al., 2024). In vitro it kept collagen I, elastin and fibronectin gene expression up in fibroblasts exposed to hydrogen peroxide (Chae et al., 2023). No study of Gly-Pro-Hyp applied to skin was found.

Benefits

Preserved collagen I, elastin and fibronectin gene expression under oxidative stress (fibroblasts, in vitro), reduced UV-induced skin damage after oral dosing (mouse); no topical data

Dosing reference

Research dose: Topical; no published topical concentration or human dose.

Topical only as sold. No topical concentration has been published. Animal studies dosed it orally or IV (rat: 5 mg/kg IV, 100 mg/kg intragastric for PK).

Mechanism

Proposed. Gly-Pro-Hyp prevented the hydrogen-peroxide-induced drop in COL1A, elastin and fibronectin gene expression in dermal fibroblasts (Chae et al., 2023). In UV-exposed mice given it orally, network analysis suggested JUN, FOS, IL-17 and TNF signaling, which was not tested directly (Yang et al., 2024). Repeats of the (Gly-Pro-Hyp)n motif in collagen bind keratinocyte growth factor (Ruehl et al., 2002). In mouse skin, oral Gly-Pro-Hyp is largely converted to the dipeptide Pro-Hyp (Yazaki et al., 2017). The old decorin, proteoglycan and crosslinking claims have no source.

Evidence

Preclinical: animal or in vitro data only

Prevented hydrogen-peroxide-induced loss of COL1A, elastin and fibronectin gene expression in human dermal fibroblasts (Chae et al., 2023)
Oral Gly-Pro-Hyp reduced UV-induced photoaging in mice, comparable to a tripeptide-rich collagen hydrolysate on an equal-hydroxyproline basis (Yang et al., 2024)
Rat PK after IV (5 mg/kg) and intragastric (100 mg/kg) dosing: oral bioavailability 4.4%, partly converted to Pro-Hyp (Won et al., 2024)
Detected in human plasma after a tripeptide-rich collagen hydrolysate; in mice, pure Gly-Pro-Hyp raised Pro-Hyp in skin (Yazaki et al., 2017)
Human-trial status: no trial of Tripeptide-29 applied to skin; human data are oral collagen hydrolysates containing it among many peptides

References

Side effects

No topical safety study has been published. Gly-Pro-Hyp is a normal product of collagen digestion and appears in human blood after collagen hydrolysate is eaten (Yazaki et al., 2017). Commonly reported (anecdotal): mild irritation.

Storage

Storage: Room temperature, away from light
Lyophilized: 2 years at room temp
Reconstituted: N/A (ready to use)

Pharmacology

Half-life: No topical data. Rat IV and intragastric PK published, with flip-flop kinetics after oral dosing (Won et al., 2024)
Bioavailability: Topical: not measured. Oral: 4.4% absolute bioavailability in rats (Won et al., 2024)
Molecular weight: 285.3 Da
Sequence: Gly-Pro-Hyp