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What is GHK-Cu? The copper peptide, collagen and what research shows

GHK-Cu is a complex of the tripeptide glycine-histidine-lysine with a copper ion that occurs naturally in human blood, saliva and urine. In laboratory studies it increases collagen production, supports wound healing and influences the activity of thousands of genes. Its blood level falls with age, which is why it is studied mainly in connection with skin ageing. Most data come from cell cultures and cosmetic research.[4]

GHK-Cu at a glance

  • Structure: Gly-His-Lys + Cu²⁺, molecular weight about 402 g/mol, blue colour from the copper.
  • Discovery: 1973, Loren Pickart, in blood plasma.[1]
  • Plasma level: around 200 ng/ml at age 20, around 80 ng/ml at age 60.[3]
  • Uses: cosmetics (serums, creams), research on healing and ageing.

How was GHK-Cu discovered?

In 1973 the American biochemist Loren Pickart noticed that liver cells from older people behave “younger” in the presence of blood plasma from young donors – they produce proteins much like young cells. Behind this effect was a small tripeptide, GHK, which was present at a higher concentration in young people’s plasma.[1] It later turned out that GHK has a strong affinity for copper and occurs in the body mainly as the GHK-Cu complex.

Why does GHK-Cu contain copper?

Copper is essential for enzymes that build and strengthen connective tissue – for example lysyl oxidase, which cross-links collagen and elastin fibres, or superoxide dismutase, which protects cells from oxidative stress. Free copper, however, is toxic to cells. GHK acts as a “carrier”: it binds copper tightly and delivers it safely where it is needed.[3]

How does GHK-Cu act on the skin?

A key 1988 study showed that GHK-Cu increases collagen production in cultures of skin fibroblasts at nanomolar concentrations – amounts that match natural levels in the body.[2] Further work described effects on the production of elastin, glycosaminoglycans (substances that hold water in the skin) and on enzymes that break down damaged collagen. GHK-Cu therefore speeds up not only the building but also the “clean-up” of tissue.[4]

ProcessWhat GHK-Cu influenced in studiesModel
Collagen productionIncreased collagen synthesis[2]Skin fibroblasts
Tissue remodellingMetalloproteinases and their inhibitors[4]Cells, animals
Wound healingFaster closure, blood vessel formation[4]Animals
Oxidative stressAntioxidant action[3]Cells, animals
Hair growthHair follicle size[6]Mice

What do the gene data say?

Pickart and colleagues analysed GHK using the Connectivity Map database, which shows how different substances change the activity of human genes. According to their analysis, GHK markedly changes the expression of roughly a third of human genes – many of them related to DNA repair, antioxidant defence and tissue remodelling. The authors interpret this as GHK shifting gene activity “back” towards a younger profile.[5] However, this is a computational analysis on cell lines, not proof of an effect in humans.

Does GHK-Cu help hair?

A mouse study from the 1990s described copper peptides enlarging hair follicles and promoting fur growth.[6] Many cosmetic hair products build on this work. Controlled studies in people with hair loss are missing from the scientific journals, however.

What are the human data?

In humans, GHK-Cu has been studied mainly topically – in creams and serums. Manufacturers’ cosmetic studies describe improved skin firmness and fine lines after several weeks of use, but these were mostly small studies outside peer-reviewed journals.[4] Injectable use in humans has not been studied systematically.

What are the side effects of GHK-Cu?

When applied to the skin, GHK-Cu is considered safe and only rarely causes irritation. With the injectable form, injection-site reactions and bluish skin discolouration at higher concentrations, related to the copper, have been described. Because GHK-Cu carries copper, it is not suitable for people with copper metabolism disorders such as Wilson’s disease.

What is the difference between GHK and GHK-Cu?

GHK is the tripeptide alone without the metal; GHK-Cu is its complex with copper. Thanks to its high affinity for copper, GHK in the blood is found mostly bound to it. Most studies on collagen production and healing worked with the GHK-Cu complex, while some newer gene analyses concern GHK alone. For research it is therefore important to know which form a study used.[5]

Why is GHK-Cu blue?

Its blue colour comes from divalent copper ions, much like copper sulphate. Lyophilized GHK-Cu is therefore a blue to blue-violet powder and its solution is blue. A change in colour to green or brown may indicate degradation or impurities. The blue skin discolouration described with injectable use is caused by the copper at the injection site.

How is GHK-Cu used in cosmetics?

In cosmetic products GHK-Cu is added to serums, creams and hair products, usually at low concentrations. Because the copper complex can react with strong acids and antioxidants, manufacturers often recommend not using it in the same step as products high in acids or vitamin C. Cosmetic use on the skin is the best-researched area of GHK-Cu.[4]

Is GHK-Cu studied beyond the skin?

Yes. Pickart and colleagues published a review summarising GHK’s effects on oxidative stress, inflammation and nerve tissue and proposing a role in protecting against age-related degenerative changes, including in the brain.[3] These are, however, mainly hypotheses based on cell and animal data and gene analyses. Clinical studies outside cosmetics and wound healing are lacking.

Animal studies also looked at wound healing in models with poorer blood supply, where GHK-Cu supported blood vessel formation and wound closure.[4]

Summary

  • GHK-Cu is the natural tripeptide Gly-His-Lys with bound copper, whose blood level falls with age.[3]
  • Even at nanomolar concentrations it increases collagen production in cells and supports tissue remodelling.[2]
  • In animals it speeds up wound healing, and according to gene analyses it influences the activity of a large share of human genes.[4][5]
  • It is used mostly in cosmetics; controlled studies in humans outside cosmetics are lacking.

Frequently asked questions

Is GHK-Cu safe for the skin?

In cosmetic use it is considered well tolerated, and irritation is rare. People with copper metabolism disorders should not use it.

How much GHK-Cu is in the human body?

Young adults have around 200 ng/ml in their blood plasma; at age 60, around 80 ng/ml.[3]

Does GHK-Cu help with scars?

Animal studies describe faster healing and better tissue remodelling. Controlled studies in people with scars have not been published, however.

Why do GHK levels fall with age?

The exact cause is not known. The decline is linked to general changes in blood proteins during ageing, and it is one of the reasons GHK is studied in connection with skin ageing.

How is GHK-Cu stored?

Lyophilized powder cool and dark, long term in the freezer. The solution belongs in the fridge and is more sensitive to light; a change from blue to green or brown may indicate degradation.

For laboratory research we offer GHK-Cu 50 mg with a certificate of analysis from an independent laboratory and a safety data sheet.

Sources

  1. Pickart L, Thaler MM. Tripeptide in human serum which prolongs survival of normal liver cells and stimulates growth in neoplastic liver. Nature New Biology. 1973;243(124):85–87. PubMed ↗
  2. Maquart FX, et al. Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. FEBS Letters. 1988;238(2):343–346. PubMed ↗
  3. Pickart L, et al. The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging: implications for cognitive health. Oxidative Medicine and Cellular Longevity. 2012;2012:324832. PubMed ↗
  4. Pickart L, Vasquez-Soltero JM, Margolina A. GHK peptide as a natural modulator of multiple cellular pathways in skin regeneration. BioMed Research International. 2015;2015:648108. PubMed ↗
  5. Pickart L, Margolina A. Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data. International Journal of Molecular Sciences. 2018;19(7):1987. PubMed ↗
  6. Uno H, Kurata S. Chemical agents and peptides affect hair growth. Journal of Investigative Dermatology. 1993;101(1 Suppl):143S–147S. PubMed ↗

The information in this article is for educational purposes only and does not replace medical advice. The substances described are not approved medicines, and Jolt Peptides products are intended solely for laboratory research, not for use in humans or animals.

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