In Plain English:
Tripeptide-29 is the most abundant repeating unit in human collagen — the three-amino-acid sequence Glycine-Proline-Hydroxyproline. Applying it topically or ingesting it orally tells fibroblasts that collagen has degraded and new synthesis is needed. At 285 Da it is small enough to penetrate into the upper dermis without a delivery carrier. Manufacturer in-vitro data shows a 400% increase in Type I collagen synthesis at 3% concentration after 48 hours. Human trials on structurally related collagen tripeptide formulations (1 g/day oral, 4–12 weeks) consistently show reduced wrinkle depth, improved skin elasticity, and restored barrier hydration.
Research Maturity
Limited Human (400+ PubMed results on Gly-Pro-Hyp / collagen tripeptide; no standalone Tripeptide-29 human RCT+ Studies)
Focus
Skin & Aesthetics
Soft Tissue Support
Origin
Gly-Pro-Hyp is the canonical repeating triplet of native human collagen — found in all fibrillar collagens (Types I, II, III). The synthetic cosmetic ingredient is produced by solid-phase peptide synthesis from non-animal, non-GMO amino acid precursors (hydroxyproline often derived from seaweed-sourced hydroxylation). CAS 2239-67-0. INCI name: Tripeptide-29. Listed on COSMILE Europe and Paula's Choice-EU as an approved cosmetic active. Not to be confused with CAS 92113-31-0 (Lotioncrafter solution designation which reflects formulation, not the pure peptide).
Mechanism
Acts as a matrikine — a collagen fragment that binds fibroblast receptors (CD44, α2β1 integrin, DDR1/DDR2) and activates TGF-β/Smad and MAPK/ERK signalling cascades, upregulating collagen Type I and III gene expression. Hydroxyproline residue stabilises the collagen triple-helix and confers resistance to MMP-1 and MMP-3 degradation. May inhibit dipeptidyl peptidase-IV (DPP-IV), reducing extracellular matrix turnover. Separately, inhibits accumulation of advanced glycation end-products (AGEs) and reduces oxidative stress markers. Oral route: absorbed intact via PEPT1 transporter in the small intestinal brush-border membrane; Gly-Pro-Hyp and its dipeptide hydrolysis product Pro-Hyp appear in plasma within 30–60 min and accumulate preferentially in dermal tissue.
Outcome
Topical RCT (Lee et al. 2022, n=22, 4 wks twice-daily): periorbital roughness −7.4% (p<0.001), gross elasticity +2.5% (p<0.001), skin density +7.2% (p<0.001), AGEs −4.4% (p<0.001); 95.5% satisfaction, zero adverse events. Oral RCT (Shin et al. 2021, n=73, 1 g/day, 12 wks): significant reduction in deep wrinkle parameters Rmax, Rp, Rv vs. placebo at week 12; skin capacitance (moisture) significantly increased. Oral RCT (Tak et al. 2021, n=84, 1 g/day, 12 wks): TEWL significantly reduced vs. placebo (p<0.05) after adjustment for climate variables; hydration improved particularly in women under 50. Murine photoaging study (Yang et al. 2024, Food & Function): Gly-Pro-Hyp-enriched hydrolysate (11.4% tripeptide) achieved 65× higher plasma AUC for Gly-Pro-Hyp than low-tripeptide control, with superior reduction of MMP-1/MMP-3 and improved epidermal thickness vs. UV-only controls. In-vitro: 3% concentration → +400% Type I collagen synthesis at 48 h (manufacturer data, Active Peptide Company).
