Tripeptide-1 and Tripeptide-29

Tripeptide-1: GHK, glycyl-L-histidyl-L-lysine, "copper-free GHK". Tripeptide-29: Gly-Pro-Hyp (GPO), glycyl-prolyl-hydroxyproline, "collagen tripeptide"

Skin & cosmetic

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Summary

Class: Tripeptide-1: naturally occurring human plasma tripeptide, here without a bound copper ion. Tripeptide-29: the single most common three-amino-acid repeat in collagen, synthesised or isolated from collagen hydrolysate
Mechanism: GHK: signals fibroblast repair and binds copper already present in skin; GPO: acts as a collagen "building block" and matrikine signal to fibroblasts
Routes studied: Topical (both); oral for GPO-type collagen tripeptides (see Collagen peptides profile)
Dose range reported: Topical GHK (non-copper): typically 0.01–1% in serums. Tripeptide-29: 0.5–3% in some "collagen-building" serums †. Oral collagen tripeptide preparations rich in GPO: 1–3 g/day in trials
Half-life: GHK: plasma clearance within hours if injected; topical, not applicable. GPO: detected in plasma for several hours after oral collagen intake
Storage: Finished products: room temperature. Raw peptides: refrigerate, protect from moisture
Regulatory status: Both permitted cosmetic ingredients; GPO-rich collagen peptides are also sold as food supplements; no medicinal approval

Doses are as reported in studies or by the community — never recommendations.

1What it is

This profile covers two small peptides that sit alongside GHK-Cu (#5) in cosmetic formulas and are often confused with it.

Tripeptide-1 is GHK without the copper. In the body GHK exists in equilibrium with copper and other metals; Loren Pickart, who discovered it, argued that the copper complex is the active form and that "copper-free" GHK applied to skin simply picks up copper from the tissue. Cosmetic brands sell both forms; the non-copper version is colourless (the copper complex is blue), cheaper and less likely to react with vitamin C and acids, which is the main reason it exists as a separate ingredient. Palmitoyl tripeptide-1 (#181) is the same sequence with a fatty-acid tail.

Tripeptide-29 is Gly-Pro-Hyp, the repeating unit that makes up a large fraction of collagen. Hydroxyproline (Hyp) is almost unique to collagen, so this tripeptide is essentially a "collagen signature". It appears in blood after people eat collagen hydrolysate, and it is also made synthetically for topical use. In cosmetics it is marketed as a collagen "precursor" or "mimetic".

Both are naturally occurring molecules.

2How it's thought to work

GHK. the same matrikine and gene-expression story as GHK-Cu — fibroblast activation, collagen and glycosaminoglycan synthesis, antioxidant enzyme support — with the caveat that most of the mechanistic work used the copper complex. Whether GHK acquires enough copper in skin to behave identically is argued but not demonstrated.

Tripeptide-29. two ideas. First, that Gly-Pro-Hyp and the related dipeptide Pro-Hyp act as signals: fibroblasts exposed to these fragments increase proliferation, hyaluronic acid and collagen synthesis in culture (Ohara 2010 and related Japanese work). Second, a "raw material" argument — that supplying the building block helps collagen assembly — which is biochemically weak for topical use because skin is not short of amino acids.

The unpalmitoylated collagen fragment. Without the fatty tail it penetrates the stratum corneum poorly, which is the main argument for the lipopeptide versions.Schematic — not to scale

3What the research shows

Graded B/D

GHK (non-copper), topical skin ageing

Nearly all published human data concern GHK-Cu (see #5). Studies of copper-free GHK in skin are limited to cell culture and the Broad Institute gene-expression analyses (Pickart 2015, 2018), plus small manufacturer product tests of serums containing tripeptide-1 among other actives. No controlled human trial of non-copper GHK alone has been found. [1][2]

Tripeptide-29, fibroblast stimulation

Cell studies show Pro-Hyp and Gly-Pro-Hyp increase fibroblast proliferation and migration and alter hyaluronic acid synthesis (Shigemura 2009, J Agric Food Chem — Pro-Hyp; Ohara 2010, J Dermatol). Rodent work shows Gly-Pro-Hyp administered orally reaches skin and may support collagen density (Yazaki 2017, J Agric Food Chem). [3][4][5]

Graded B/—

Tripeptide-29, topical skin outcomes

Ingredient-manufacturer studies of GPO-containing serums report improved hydration and elasticity over 4–8 weeks in small volunteer groups †. No peer-reviewed, placebo-controlled topical trial of tripeptide-29 alone was found.

Graded A/B

Oral collagen tripeptides (GPO-rich)

Oral collagen hydrolysates and "collagen tripeptide" preparations have randomised, placebo-controlled trials reporting modest improvements in skin hydration and elasticity (Proksch 2014, Skin Pharmacol Physiol; Choi 2014, J Cosmet Laser Ther — a collagen tripeptide study †). These are industry-funded and short, and they concern the oral route, which belongs to the Collagen peptides profile; they are mentioned here because the same molecule is involved. [6]

4Reported side effects and interactions

Literature-reported

Topical GHK and GPO are well tolerated in cosmetic testing; no sensitisation signal. Oral GPO-rich collagen is generally well tolerated with occasional GI upset.

Community-reported

copper-free GHK is often chosen precisely because it does not sting or stain like injectable or high-strength GHK-Cu; few complaints. Tripeptide-29 serums: none notable.

Theoretical. none specific. Fish- or bovine-derived collagen tripeptide raises allergen labelling issues in food products, not in synthetic cosmetic GPO.

Interactions. non-copper GHK is compatible with vitamin C and acids where GHK-Cu may not be; this is a formulation convenience, not a safety issue.

Markers researchers commonly monitor

No compound-specific blood markers for topical use. For oral GPO-rich collagen, trials measured skin hydration and elasticity, not blood values. Practical measures:

Marker	Why it's watched
Standardised photographs every 2–4 weeks
Corneometry / elasticity (cutometer)	the usual cosmetic trial endpoints.
Serum copper is not relevant for non-copper GHK at topical doses (contrast with injectable GHK-Cu, #5)
Forearm patch test before first use

Free for everyone. Safety information is never behind a paywall.

5Formulation and handling

Both are water-soluble powders used at fractions of a percent to a few percent in water-based serums; both are heat-sensitive and added in the cool-down phase. Tripeptide-1 (non-copper) is colourless and does not discolour with ascorbic acid. Members who DIY report dissolving GHK in distilled water or a glycol at 0.1–1%, refrigerating, and using within a few weeks; this is community practice, not a tested protocol. No calculator applies for topical use; injectable GHK without copper is not a documented practice and is not covered here.

6Commonly studied alongside

GHK-Cu (#5, the copper complex and the main evidence base), palmitoyl tripeptide-1 (#181), collagen peptides (oral), vitamin C derivatives (GHK compatibility rationale), hyaluronic acid.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Both are cosmetic ingredients; GPO-type collagen peptides also sold as dietary supplements (GRAS/self-affirmed collagen hydrolysate)
European Union	Tripeptide-1 and tripeptide-29 CosIng-listed; permitted. Collagen hydrolysate is a permitted food ingredient; novel-food status of isolated synthetic GPO as a food is unclear †
United Kingdom	Same as EU
Australia	Permitted cosmetic ingredients; oral collagen regulated as food or listed complementary medicine depending on claims
South Africa	Permitted in cosmetics; oral collagen sold as a food supplement
Sport (WADA)	Not listed

8Open questions

Does copper-free GHK on skin become GHK-Cu in situ, and does it then match the copper complex's effects? Argued, not shown.
Is topical Gly-Pro-Hyp absorbed into the dermis at all? No penetration study found.
Any independent, placebo-controlled trial of either peptide alone as a topical? None found.

9References

1Pickart L, Vasquez-Soltero JM, Margolina A (2015). GHK peptide as a natural modulator of multiple cellular pathways in skin regeneration. Biomed Res Int. PubMed · DOI
2Pickart L, Margolina A (2018). Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data. Int J Mol Sci. PubMed · DOI
3Shigemura Y et al. (2009). Effect of prolyl-hydroxyproline (Pro-Hyp), a food-derived collagen peptide in human blood, on growth of fibroblasts from mouse skin. J Agric Food Chem. PubMed · DOI
4Ohara H et al. (2010). Collagen-derived dipeptide, proline-hydroxyproline, stimulates cell proliferation and hyaluronic acid synthesis in cultured human dermal fibroblasts. J Dermatol. PubMed · DOI
5Yazaki M et al. (2017). Oral ingestion of collagen hydrolysate leads to the transportation of highly concentrated Gly-Pro-Hyp and its hydrolyzed form of Pro-Hyp into the bloodstream and skin. J Agric Food Chem. PubMed · DOI
6Proksch E et al. (2014). Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study. Skin Pharmacol Physiol. PubMed · DOI

† Being confirmed by our reviewers against current sources.

10Community

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11Page history

31 Oct 2026Profile published — awaiting medical review

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