GHK-Cu: what do we know about skin, hair and tissue repair?

There are indications that GHK-Cu affects skin, hair follicles and tissue repair. They come predominantly from cell and animal studies. Human studies mainly concern topical cosmetic use and wound care. Robust human studies have not yet established whether GHK-Cu injections improve skin, hair growth or tissue healing, or whether they are safe.

What is GHK-Cu?

GHK-Cu is a compound of copper and the tripeptide glycyl-L-histidyl-L-lysine. “Tripeptide” means that three amino acids are joined together. GHK-Cu occurs naturally in the body, and its concentration declines with age. It is among the more frequently studied copper peptides.

The focus here is injectable GHK-Cu as offered in wellness settings for skin, hair and tissue repair. This use is intended to have systemic effects—throughout the body. For topical cosmetic use, it appears under the ingredient name copper tripeptide-1. The US FDA has not approved GHK-Cu as a systemically administered medicine.

How does GHK-Cu work?

In cell and animal models, GHK-Cu influences several processes involved in tissue remodeling. The effects studied include:

• Changes in the extracellular matrix, the material between cells;
• Copper delivery;
• Antioxidant and anti-inflammatory effects;
• The formation of new blood vessels;
• Activation of gene programs involved in repair processes. 1

These findings explain possible mechanisms. They do not establish whether systemic use also benefits humans.

Is GHK-Cu FDA-approved?

No. The US Food and Drug Administration has not approved GHK-Cu as a medicine for injection or any other systemic use.

Compounding—the preparation of customized formulations in the United States—is a separate issue. For copper peptides, this is an area of regulatory dispute. The information underlying this article does not reliably establish which forms of preparation are lawful. Separate rules for cosmetic ingredients apply to topical cosmetic use.

What does the research show?

Research on systemic use is preclinical: it investigates GHK-Cu in cells and animals before conclusions can be drawn about treatment in humans. The animal studies show effects under specific experimental conditions.

Model	Result
Rat	Injected GHK-Cu temporarily improved the healing of a ligament graft. 2
Mouse	GHK-Cu reduced acute lung injury. 3
Human	The data mainly concern topical cosmetic applications and wound care. Robust human studies establishing the efficacy or safety of injected GHK-Cu for skin, hair or tissue repair are lacking.

These results suggest a possible benefit from GHK-Cu injections in humans, but do not demonstrate one.

Frequently asked questions

What is GHK-Cu, and how does it work in the body?

GHK-Cu is a naturally occurring complex of three amino acids—glycine, histidine and lysine—and a copper(II) ion. Together, the amino acids form the copper-binding tripeptide GHK. It was first identified in human blood plasma in the 1970s.

Its plasma concentration falls with age. Reported values are approximately 200 ng/mL at age 20 and about 80 ng/mL at age 60. The unit means nanograms per milliliter. 4

In laboratory and animal studies, GHK-Cu influences matrix metalloproteinases (MMPs) and their inhibitors, among other targets. MMPs are enzymes that remodel the extracellular matrix, the material between cells. 5 GHK-Cu also influences genes involved in anti-inflammatory and antioxidant defenses. The findings suggest that it regulates several biological processes, rather than acting through a single pathway.

What does research show about GHK-Cu and collagen production?

Preclinical and early clinical research suggests that GHK-Cu may increase the production of types I and III collagen, sometimes at very low concentrations. Most findings, however, come from in-vitro experiments—studies outside a living organism. Human data mainly concern topical cosmetic use.

In cultured fibroblasts, the cells of connective tissue, GHK-Cu stimulated collagen production at concentrations between 10⁻¹² and 10⁻¹¹ M and above. The strongest effect occurred at 10⁻⁹ M. M denotes molar concentration in mol/L. Changes in cell numbers did not explain the increased collagen production. 6

In a rat wound-chamber study, GHK-Cu increased collagen content compared with a saline control treatment. The increase depended on concentration. Messenger RNA for types I and III collagen also increased, while TGF-beta mRNA did not. Messenger RNA carries the information from a gene that a cell uses to make a protein. GHK-Cu stimulated collagen production twice as strongly as the production of other proteins. 7

An analysis of gene-expression data from the Broad Institute’s Connectivity Map reported that GHK changed the activity of 31.2% of human genes by ≥50%. Exactly what was included in the denominator “human genes” is unclear here. This finding also concerns GHK; it cannot automatically be applied to GHK-Cu. 4

In a study using thigh skin biopsies, collagen production increased in 70% of women treated with GHK-Cu. The corresponding figures were 50% in the vitamin C cream comparison group and 40% in the retinoic acid group. These percentages indicate how many women had increased collagen production, not the size of that increase. 8

How does GHK-Cu affect wound healing?

In animal studies, wounds closed faster with GHK-Cu, and inflammatory markers were lower. The extent to which these findings apply to human wound healing has received limited study. Most findings come from cell and animal experiments.

In a study involving 24 Sprague-Dawley rats, researchers applied a 2% GHK-Cu gel (Iamin) to poorly perfused wounds extending through the full thickness of the skin. Wounds with this poor blood supply are described as ischemic. By day 13, wound area had decreased by 64.5% with GHK-Cu, compared with 45.6% with the gel vehicle alone and 28.2% in untreated control wounds. 9

Concentrations of the inflammatory messenger TNF-alpha and the matrix metalloproteinases MMP-2 and MMP-9 were also significantly lower in GHK-Cu-treated wounds.

Can GHK-Cu help with thinning hair or hair loss?

For GHK-Cu itself, randomized controlled human trial data establishing a benefit for thinning hair or hair loss are lacking. Laboratory and animal studies offer indications that copper peptides may promote hair follicle activity. However, the studies cited here examined other peptide–copper compounds, or compounds not specifically identified as GHK-Cu.

In so-called fuzzy rats, the copper-binding peptide PC1031 enlarged hair follicles in a way similar to topical minoxidil. 10

In an ex-vivo study using removed human tissue, AHK-Cu promoted hair follicle elongation. This related copper tripeptide appeared to stimulate the proliferation of dermal papilla cells, part of the hair follicle, and reduce their death. 11 An earlier mouse study also described stimulation of hair follicles by peptide–copper complexes. 12

The findings do not provide direct evidence that GHK-Cu is effective for hair loss.

How does GHK-Cu compare with retinol for skin aging?

No direct comparison answering this question is provided here. Overall, there is more research on retinoids than on GHK-Cu. This group includes retinol and prescription tretinoin. The study described below investigated tretinoin, so its findings do not automatically apply to retinol.

GHK-Cu and retinoids differ in their mechanisms and tolerability. Retinoids act through retinoic acid receptors in the cell nucleus. Skin irritation is a known accompanying effect. 13

In a randomized controlled trial involving 99 people with photoaged skin, tretinoin at concentrations of 0.1% and 0.025% produced similar improvements over 48 weeks. However, redness and scaling were significantly greater with 0.1%. 14

For GHK-Cu, researchers propose effects through copper delivery and gene regulation. Three studies described as placebo-controlled each investigated topical application for 12 weeks, with 41 to 71 women in each study. They reported less skin laxity, improved clarity and firmness, and improvements in fine lines. 8

Tretinoin is available as an FDA-approved prescription retinoid. 15 However, these separate studies do not establish whether GHK-Cu works better or worse than retinol or tretinoin: the preparations, populations and study designs differ.

What anti-inflammatory effects does GHK-Cu have?

In tissue studies, GHK-Cu influences the NF-κB pathway and reduces the production of certain pro-inflammatory cytokines, which are immune-system signaling molecules. The findings mainly concern local processes within tissues. They do not establish a clinically demonstrated anti-inflammatory effect from systemic use.

In a mouse lung-injury study, GHK-Cu lowered the inflammatory messengers TNF-alpha and IL-6 by suppressing NF-κB signaling. 3 TNF-alpha also fell in ischemic rat wounds. 9

Other findings concern GHK. A 2012 analysis of the Broad Institute’s Connectivity Map examined the PC3 and MCF7 cell lines at a GHK concentration of 1 μM. In these cells, the activity of 268 genes increased and that of 167 genes decreased. 16

In rat wound tissue, GHK also increased levels of superoxide dismutase and catalase, two antioxidant enzymes. 17 Among the 13,424 genes in the Connectivity Map data, it stimulated 14 antioxidant genes. Looking only at genes whose activity changed by at least 50% in response to GHK, activity increased in 59% and decreased in 41%. 4

These results do not answer whether GHK-Cu can reduce elevated blood markers of inflammation. CRP, an inflammatory marker measured in blood, and other systemic inflammatory markers were not direct endpoints in the findings described. An anti-inflammatory effect throughout the body has therefore not been clinically established.

Sources

• Sources: a rat ligament-healing study (Journal of Orthopaedic Research, 2015, DOI: 10.1002/jor.22831 2 ) and a mouse lung-injury study (Oncotarget, 2016, DOI: 10.18632/oncotarget.11168 3 ), indexed on PubMed. This document is educational, is not medical advice or a health claim, and is not an offer to sell any product. Original reference Original reference